To Shakespeare's audience, nothing could be more devastating than the word, "plague." The Black Death saw one of the largest pandemics ever destroy whole towns and villages. In the 1936 film version of the play, Friar John is shown being delayed with Friar Lawrence's letter by being locked up in a house where plague had killed a man. In Londo, theatres and other establishments on the Left Bank were closed because of the illness. There was no cure. Symbolically then, it seems that Mercutio is not only cursing the Montagues and Capulets, but also predicting that their families will be wiped out.

Mercutio actually says this twice within a few lines, he says this because he is dying. If you think about it, after Mercutio says this, and then dies, if there wasn't before, there certainly is a curse on the two houses. Tybalt is killed, and then Romeo is banished, and finally, Romeo and Juliet both die. Romeo responds to his death, and his quote of the plague by saying, "This day's black fate on more days doth depend;
This but begins the woe others must end."
Basically, that his death begins a patterns of murders that will conmtinue and only end in sadness