The morphologic spectrum of intestinal metaplasia was studied in 49 gallbladders that had been excised because of cholelithiasis. Based on the absence or presence of endocrine cells, the cases of intestinal metaplasia were arbitrarily divided into two groups. The gallbladders from the first group (26 cases) contained isolated or small clusters of mature goblet cells, while those from the second group (23 cases), in addition to the goblet cells, contained argyrophil and argentaffin cells and, less frequently, Paneth cells and gland-like structures similar to colonic crypts. Pseudopyloric glands and superficial gastric-type epithelium were present in both groups. Argyrophil cells outnumbered argentaffin cells by a ratio of 4 to 1. By immunocytochemical methods serotonin-containing cells were found to be the most common endocrine cells. Other endocrine cells showed immunoreactivity for somatostatin, cholecystokinin, gastrin, and pancreatic polypeptide. The presence of gut endocrine cells and Paneth cells in the pseudopyloric glands suggests that these glands are also an integral component of intestinal metaplasia of the gallbladder. The findings support the hypothesis that cholelithiasis induces the appearance of a stem endodermal cell that, in turn, may differentiate into cells with mature intestinal or gastric phenotypes.