Although infection with Strongyloides stercoralis is usually only mildly symptomatic, it can persist for many years and occasionally progress to the hyperinfection syndrome, with a resultant high mortality rate. We studied factors associated with S stercoralis infection by comparing 28 domestic cases of S stercoralis infection with 76 controls with negative stool samples for ova and parasites. The relative risk (RR) of S stercoralis infection was increased for white patients (RR = 5.6), men (RR = 3.9), and patients who had recently used corticosteroids (RR = 3.3), had a hematologic malignancy (RR = 5.28) or had prior gastric surgery (RR = 11.5). These risk factors might be for initial infection, persistence of infection, or both. Although they are not necessarily causal, knowledge of them may lead to earlier recognition of this dangerous and treatable disease.