Cryptosporidium is increasingly recognized as an important agent of diarrhea in normal and immunocompromised humans. In young children in developing countries the parasite is a cause of persistent diarrhea with an associated excess mortality. To elucidate possible determinants of cryptosporidiosis, an open cohort of young children from a semiurban area of the capital of Guinea-Bissau was followed for 2 years. Data about possible risk factors were recorded each month, and a nested case-control study of 125 children with Cryptosporidium diarrhea and an equal number of matched controls was conducted. The following risk factors were identified by conditional multiple logistic regression: keeping of pigs (odds ratio (OR) = 2.5, 95% confidence interval (CI) 1.4-4.7) and dogs (OR = 2.1, 95% CI 1.0-4.2) in the household, storage of cooked food for later consumption (OR = 1.8, 95% CI 1.0-3.3), and child's sex (OR for boys = 1.9, 95% CI 1.0-3.4). Breast feeding was protective (OR = 0.3, 95% CI 0.1-1.1). The findings provide clues for interventions against this major cause of childhood diarrhea and give suggestions for further studies.