Paul Zindel's The Effect of Gamma Rays on Man-in-the-Moon Marigolds was first produced in 1964 by the Alley Theatre in Houston, Texas. It launched his career as a serious playwright. Nina Vance, head of the Alley Theatre, was so impressed with the play that she took an immediate option on Zindel's next work. The play was also presented on television in October 1966 by the National Educational Television as part of its New York TV Theatre series. The televised version was not very well-received, however. In the Dictionary of Literary Biography, Ruth Strickland notes, "Reviewers of the television drama found little to praise.'' The version shown on television had been cut, however, and this may have caused the unenthusiastic reception.

The Effect of Gamma Rays on Man-in-the-Moon Marigolds opened off-Broadway on April 7, 1970, at the Mercer-O'Casey Theatre. This time the reviews were overwhelmingly positive. Zindel was hailed as a promising new playwright. Audiences and critics appreciated his ability to create believable teenage characters and found the story of the Hunsdorfer family very poetic and moving. Many critics compared the play to Tennessee Williams's The Glass Menagerie, noting its sensitive portrayal of human relationships. As Ruth Strickland writes, "many critics found the play old-fashioned in the best sense of the word, praising its realism, yet moved by its poetry.’’ In American Theatre 1969-1970, Clive Barnes gives the play very high praise, writing, "One of the greatest, probably the greatest, hit of the current off-Broadway season, Paul Zindel's The Effect of Gamma Rays on Man-in-the-Moon Marigolds, would clearly have made it equally as well on Broadway.’’ The play continued off-Broadway until a fire forced it to move into the New Theatre on Broadway. The play remained there until May 14, 1972, when it closed after 819 performances. The play won numerous prestigious awards, including a 1970 Obie Award as best play of the season, a 1970 New York Drama Critics' Circle Award as best American play of the year, and the Pulitzer Prize for Drama in 1971.

Some critics felt that The Effect of Gamma Rays on Man-in-the-Moon Marigolds was so widely accepted by audiences because it hearkened back to a more traditional format than had been seen recently on many off-Broadway stages. In the late 1960s there was a wild explosion of experimental theatre off-Broadway. Many shows had little or no story line and were not much more than a collection of random acting exercises. While some audiences appreciated the experimentation and innovation, many found it hard to make sense of these performances. Plays with a story line were easier for audiences to understand. The Effect of Gamma Rays on Man-in-the-Moon Marigolds provided a story, and therefore appealed to a wider audience. A play with a well-crafted story line is sometimes known as a "well-made play.'' Zindel’ s play can be considered a well-made play, and Clive Barnes notes this feature in American Theatre 1969-1970 as part of its appeal: "The off-Broadway show that was most successful was Paul Zindel's The Effect of Gamma Rays on Man-in-the-Moon Marigolds. Interestingly, it is almost completely a model of the well-made play, a family drama of the kind we thought had gone out with Arthur Miller and Tennessee Williams.''

One criticism that has been leveled against the play is that it is melodramatic and overly sentimental. While most critics have appreciated the gentle tone of the piece, some feel that Zindel is a bit too sappy in his presentation of the family's situation. Ruth Strickland notes that Zindel's ‘‘weaknesses are lapses into melodrama’’ and, in the Concise Dictionary of American Literary Biography, Jack Forman describes the piece as "a domestic melodrama with an occasional lapse into sentimentality.’’ Overall, though, the response of audiences and critics alike has been positive. In his recent book Hot Seat: Theater Criticism for the New York Times, 1980-1993, Frank Rich notes that he finds the play "compassionate," and he appreciates that Zindel avoids ‘‘simple moral judgments.’’ The play is still performed in regional theatres throughout the country, a testament to its quality and the universality of its themes.