To study whether African-Americans are less likely than whites to present with cryptosporidiosis as an AIDS-defining condition (ADC), a case-control study was conducted using a large, population-based surveillance registry of AIDS patients in California. Data from January 1980 through June 1999 were analysed using risk factor stratification and multivariate logistic regression to evaluate confounding by other risk factors such as gender, injection drug use (IDU), CD4 counts, age and sexual orientation. Cases included 1373 subjects with cryptosporidiosis as an ADC and controls included 97419 subjects with other ADC. The results indicate a significantly lower risk for presentation with cryptosporidiosis as an ADC among African-Americans compared with whites (OR vs. whites = 0·5, 95% CI 0·4, 0·7). Additionally, there is evidence that heterosexuals are less likely than homosexual/bisexual males to present with cryptosporidiosis (OR = 0·5, 95% CI 0·4, 0·7). Our analyses also suggest a decreasing risk with increasing age. The possibility that there may be biologic factors or differential lifetime exposures that account for the difference between the racial/ethnic groups merits further investigation.