To test the effects of paromomycin, 10 patients with AIDS and cryptosporidiosis were randomized to paromomycin or placebo in a double-blind trial. After 14 days, patients were switched to the other treatment for 14 additional days. Measures included the number and character of each stool and weekly 24-h stool specimens for weight and oocyst excretion. During the paromomycin treatment phase, oocyst excretion decreased from 314 X 106 to 109 X 106 /24 h (P<.02). Oocyst excretion increased for the 4 patients initially on placebo compared to a median decrease of 128 X 106 /24 h for the 6 initially treated with drug (P<.02). Stool frequency also decreased more in those treated with drug (3.6 fewer vs. 1.25 fewer/24 h, P<.05). Trends favored drug over placebo for stool weight, stool character, and Karnofsky score. Paromomycin treatment resulted in improvement in both clinical and parasitologic parameters in cryptosporidiosis in AIDS. © 1994 The University of Chicago Press.