The effect of calcitonin (CT) and the interaction of vitamin D and prostaglandin E2 with CT on renal tubular calcium reabsorption was examined in conscious, restrained thyroparathyroidectomized (TPTX) rats. Each rat was infused with a medium containing a fixed concentration of Ca (0-30 mM) to obtain steady-state serum and urinary Ca before CT administration. Constant infusion of CT (0.01-0.5 U/h) caused a dose-dependent reduction in serum and urinary Ca excretion within 2 h and reached another steady state. There were no significant changes in inulin clearance in any groups of animals before and after CT administration. By plotting urinary Ca excretion against-serum Ca, the effect of CT on tubular Ca reabsorption can be estimated. In vitamin D-replete rats, 0.05 U/h CT as well as 0.5 U/h CT caused a stimulation of tubular Ca reabsorption. In vitamin D-deficient rats, tubular reabsorptive capacity for Ca is much lower than that in vitamin D-replete rats. Furthermore, stimulation of tubular Ca reabsorption was observed only with a high dose (0.5 U/h) of CT. Simultaneous administration of 20 micrograms/h prostaglandin E2 (PGE2), that caused an inhibition of CT-induced stimulation of 1,25-dihydroxyvitamin D3, 1,25(OH)2D3, synthesis and phosphaturia [Endocrinology 116: 693-697, 1985], did not affect the effect of CT on the renal tubular Ca reabsorption. These results demonstrate that CT stimulates renal tubular Ca reabsorption, and that vitamin D status modulates the responsiveness of renal tubules to CT.(ABSTRACT TRUNCATED AT 250 WORDS)