Recent studies have indicated that solitary or multiple gallstones may differ with respect to the conditions favoring their formation, such as nucleation time. We examined the clinical, histological and laboratory characteristics of symptomatic gallstone disease in a series of 125 consecutive patients with either solitary (n = 33) or multiple (n = 92) cholesterol gallstones undergoing cholecystectomy. The nature of biliary pain was found to differ in the two groups. Histological diagnoses of acute cholecystitis and gallbladder cancer was more frequent in the patients with multiple stones, and cholesterolosis in those with solitary stones. Furthermore, the stone cholesterol content was higher in the solitary stone group than in the multiple stone group. Morbid complications such as cholangitis and pancreatitis were rare and occurred only in the multiple stone group. The results support the view that gallbladder disease presents histological evidence of biliary complications more often in patients with multiple cholesterol stones than in those with solitary stones.