A prospective case-control study was carried out to determine if there was a true association between diverticular disease of the colon and cholelithiasis. The prevalence of gallstones was higher in 102 patients with diverticular disease of the colon (45%) than in 102 control subjects, matched for age, sex, body weight, and number of pregnancies (22%) (P less than 0.001). The difference was only significant in women. Although these results obtained in hospitalized patients cannot be generalized to the population at large, this study suggests an association between diverticular disease of the colon and gallstone disease. The possibilities of referral bias, detection bias, and chance are considered, and the mechanism of this association is discussed, with particular reference to the role of a fiber-depleted diet.