Total gastrectomy or resection of the acid-producing part of the stomach (fundectomy) in the rat induced a marked and rapid reduction in bone wet weight, ash weight, and density (expressed as ash weight in mg/mm3 bone). Bone volumes were also affected but not as much. The radius, sternum, tibia, and femur were studied. Three weeks after gastrectomy the bone ash weight was reduced by almost 30% and the density by more than 25%. Maximum bone loss (approximately 40%) occurred about 6 weeks after the operation. The bone loss after gastrectomy was somewhat greater than that after fundectomy, whereas antrectomy had a marginal effect only. The percentage trabecular bone volume, calculated from morphometric analysis of histologic sections of the tibia, was greatly reduced by gastrectomy (approximately 50%), somewhat less so by fundectomy, whereas antrectomy had little effect. We set out to study whether calcium malabsorption could explain the bone loss after gastrectomy. Gastric acid is thought to facilitate the intestinal absorption of ingested calcium by mobilizing calcium from insoluble complexes in the diet. The possibility that lack of acid might contribute to the bone loss after gastrectomy was examined in experiments in which the proton pump inhibitor omeprazole was given for 4-8 weeks at such a dose (400 mumol/kg/day) that acid secretion was blocked almost completely during the period of study. This treatment was without effect on bone. However, the possibility could not be excluded that gastrectomized rats develop calcium deficiency for some reason other than lack of acid.(ABSTRACT TRUNCATED AT 250 WORDS)