Although 10%-15% of patients with AIDS in the United States may acquire cryptosporidium infection, little data exist on clinical or histological characteristics that differentiate clinical outcomes. A case-control study of 83 HIV-positive adult patients with cryptosporidiosis was conducted, as was a histopathologic review of data on gastrointestinal biopsy specimens from 30 patients. Four clinical syndromes were identified: chronic diarrhea (36% of patients), choleralike disease (33%), transient diarrhea (15%), and relapsing illness (15%). A multivariate analysis of data for cases and controls revealed that acquiring cryptosporidiosis was associated with the presence of candidal esophagitis (odds ratio [OR], 2.53; P < .002) and Caucasian race (OR, 6.71; P = .0001) but not with sexual orientation. Cases had a significantly shorter duration of survival from the time of diagnosis than did controls (240 vs. 666 days, respectively; P = .0004), which was independent of sex, race, or or injection drug use. Antiretroviral use was protective against disease (OR, 0.072; P = .0001). All four clinical syndromes were represented among the histological data. There was no statistically significant correlation between histological intensity of infection and clinical severity of illness.