It has previously been proposed that the hypocalcemic action of gastrin was mediated by a gastric peptide gastrocalcin which enhanced bone uptake of calcium (Ca). The present study, thus, aimed to reconfirm the effect of gastrin on muscle and bone Ca uptake and to evaluate a possible direct effect of gastrin on tissue Ca uptake. First, we showed that human and rat gastrin (100 microgram /100 g body weight (bw), s.c.) acutely increased uptake of intragastrically administered 45 Ca by the tibia and femur. Interestingly, human gastrin was more effective and also enhanced 45 Ca uptake by the gastrocnemius muscle. In order to find out whether gastrin could act directly on bone, 10 microgram of rat gastrin /100 g bw and 45 Ca were injected into the right femoral artery supplying the right leg while the left leg received normal saline and an equal amount of 45 Ca. At 30 min, the right gastrocnemius muscle and femur were found to contain 168% and 162%, respectively, more 45 Ca than the left leg. In contrast, daily administration of 25 microgram of rat gastrins /100 g bw, s.c., for 2 weeks had no effect on muscle or bone total Ca content while the content of 45 Ca given on days 12 and 13 was lower in the tibia and femur of gastrin-treated rats. It could be concluded that gastrin transiently enhanced Ca uptake by muscle and bone. However, two-week treatment with gastrin appeared to accelerate the bone turnover rate i.e., enhanced uptake and release of calcium, so that there were not no net changes in bone total Ca content at the end of the experimental period.