It has been suggested that gallbladder removal may protect against subsequent development of myocardial infarction because of increased gastrointestinal cholesterol excretion resulting from increased enterohepatic cycling. To test this hypothesis, the authors used data from two large case-control studies of myocardial infarction--one conducted in 1976-1979 in 155 US hospitals and one conducted in 1980-1983 in 78 US hospitals. First, 550 female myocardial infarction cases were compared to 1,658 controls. Simultaneously adjusting for possible confounding variables using logistic regression, the odds ratio for development of a myocardial infarction subsequent to cholecystectomy was 0.8 (95% confidence interval, 0.5-1.1). Second, 1,511 male myocardial infarction cases were compared to 3,837 controls. With similar adjustments, the odds ratio was 0.8 (95% confidence interval, 0.5-1.2). The risk did not decline as the interval following cholecystectomy increased. The present data are compatible with a protective effect of cholecystectomy on the risk of subsequent myocardial infarction, but they are not conclusive.