Macbeth's paranoia seems to begin with Banquo's hurriedly leaving Macbeth's castle with his son, Fleance. Banquo was present when the witches predicted Macbeth's rise to royalty, and Banquo--although he hasn't discussed it with Macbeth--suspects that Macbeth "play'd most foully for it." After Banquo departs, promising to return for the banquet that evening, Macbeth soliloquizes:
To be thus is nothing;
But to be safely thus.--Our fears in Banquo
Stick deep; and in his royalty of nature
Reigns that which would be fear'd: 'tis much he dares;
And, to that dauntless temper of his mind,
He hath a wisdom that doth guide his valour
To act in safety. There is none but he
Whose being I do fear.
In other words, if Banquo hasn't already figured out exactly how Duncan was murdered, he is most likely to, and he's the sort of man who will declare it to the world, being an honorable man and loyal subject to the former king. Thus, Macbeth hires murderers to slaughter Banquo and his son (the son because Banquo's progeny has been predicted to rule while Macbeth will have a "fruitless throne," and Macbeth is none to pleased about this).
That evening, when the first murderer returns during the banquet to report, he tells him that Banquo is dead but Fleance has escaped. This fuels Macbeth's paranoia: "There the grown serpent lies; the worm that's fled / Hath nature that in time will venom breed, / No teeth for the present." That is, Fleance is too young now to be a real threat, but must be destroyed soon.
Macbeth becomes far more paranoid when the spectre of Banquo appears at the banquet that night, gory from his murder. After Banquo's ghost has made him look like a raving lunatic, Macbeth says, "It will have blood; they say, blood will have blood." It's fair to say that Banquo's ghost, then--real or imagined--contributes mightily to Macbeth's paranoia.
Later, in Act II Scene 4, Macbeth notices that Macduff hasn't appeared, either: "Macduff denies his person / At our great bidding." The king, having invited Macduff, rightfully expects Macduff to appear, but he's a no-show--more reason for paranoia.
By this point, Macbeth has gone too far to stop, and he knows it: "I am in blood / Stepp'd in so far that, should I wade no more, / Returning were as tedious as go o'er."