Four patients, all sisters, presented a long-standing history of pain in the gallbladder region and no calculi. All were first thoroughly investigated and then relieved of their symptoms by cholecystectomy. This prompted an investigation of their family over three generations, which revealed a surprisingly large number of relatives, mostly female, with acalculous gallbladder disease. Our review of various syndromes causing pain in the gallbladder region, including biliary dyskinesia, cystic duct syndrome, and chronic acalculous cholecystitis, makes a case for the existence of familial incidence of noncalculous and calculous gallbladder disease, possibly related to the disturbance of the autonomic nervous system affecting emptying of the gallbladder.