To determine factors associated with isosporiasis in persons with acquired immunodeficiency syndrome (AIDS) in Los Angeles County, data from the AIDS surveillance registry were analyzed for the eight-year period 1985-1992. Isosporiasis was reported in 127 (1.0%) of 16,351 persons with AIDS during the study period. Prevalence of infection was highest among foreign-born patients (3.2%), especially those from El Salvador (7.4%) and Mexico (5.4%), and in all persons of Hispanic ethnicity (2.9%). Persons with a history of Pneumocystis carinii pneumonia (PCP) were less likely than PCP-negative patients to have isosporiasis (0.2% and 1.4%, respectively, P < 0.01). A decrease in the prevalence of isosporiasis in patients negative for PCP was observed beginning in 1989 (P = 0.02). Prevalence decreased with age (P < 0.01, by chi-square test for trend). After controlling for multiple factors by logistic regression, isosporiasis was more likely to occur in foreign-born patients than in those born in the United States (adjusted odds ratio [OR] = 5.8, 95% confidence interval [CI] 3.4, 9.9, P < 0.001) and in Hispanics than in whites (non-Hispanics) (adjusted OR = 3.5, 95% CI 1.7, 7.2, P < 0.001). A prior history of PCP continued to be negatively associated with isosporiasis (adjusted OR = 0.2, 95% CI 0.1, 0.3, P < 0.001). Age and time remained independently associated with infection. These data suggest that isosporiasis among persons with AIDS in Los Angeles County may be related to travel exposure and/or recent immigration and that the use of trimethoprim-sulfamethoxazole (TMP-SMX) for PCP may effectively prevent primary infection or expression of latent isosporiasis. Physicians should have an increased index of suspicion for Isospora in AIDS patients with diarrhea who have immigrated from or traveled to Latin America, among Hispanics born in the United States, in young adults, and in those not receiving PCP prophylaxis. Food and water precautions should be advised and TMP-SMX prophylaxis considered for the prevention of Isospora infection for patients with human immunodeficiency virus infection who travel to Latin America and other developing countries.