To determine the occurrence and factors associated with Cryptosporidium among persons with acquired immunodeficiency syndrome (AIDS) in Los Angeles County, data were analyzed from the AIDS surveillance registry for the 10-year period 1983–1992. Among 16,953 persons with AIDS, a total of 638 (3.8%) cryptosporidiosis cases were reported during the study period. The prevalence of cryptosporidiosis was higher in persons whose suspected human immunodeficiency virus (HIV) exposure category was through sexual contact (3.9%) than among persons in other HIV exposure categories (2.6%; P < 0.01) and in immigrants from Mexico (5.2%) than in American born patients (3.8%; P < 0.01). Blacks (2.7%) were less likely than whites (4.1%) and Latinos (4.2%) to be reported with cryptosporidiosis (P < 0.001). A temporal trend was observed from 1983 to 1986 when the prevalence decreased from 6.7% to 3.6% (P < 0.001, by chi-square test for trend). After controlling for confounding variables by stratified analysis, persons whose HIV exposure was sexual (adjusted odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.3, 2.4, P < 0.01) and immigrants from Mexico (adjusted OR = 1.6, 95% CI 1.2, 2.1, P < 0.01) were more likely to have cryptosporidiosis. The negative association with black race remained significant (adjusted OR = 0.7, 95% CI 0.57, 0.96, P = 0.02). The prevalence of cryptosporidiosis decreased with age in gay and bisexual males (Mantel-Haenszel test for trend, P < 0.01) but not among female and heterosexual male cases. The temporal trend of decreasing prevalence observed was a result of a decrease in cryptosporidiosis prevalence among gay and bisexual men with AIDS from 1983 to 1986 (P < 0.01, by Mantel-Haenszel test for trend), which corresponded to a time of modified sexual behavior in this group. These data suggest the existence of modes of Cryptosporidium infection in persons with AIDS, including sexual transmission among gay and bisexual men and the occurrence of travel-related infections. Such information may be of value in recommending strategies for preventing Cryptosporidium infection in HIV-infected persons.