The influence of indomethacin on phosphaturic effect of calcitonin (CT) was examined in conscious, restrained thyroparathyroidectomized (TPTX) rats. Constant infusion of 0.5 units/h CT caused a transient phosphaturic response which peaked within 2 h after the start of the CT infusion. Indomethacin enhanced and prolonged the CT-induced phosphaturia without affecting serum phosphate levels or creatinine clearance. Because the urinary excretion of prostaglandin E2 (PGE2) was markedly suppressed by indomethacin, the potentiation of the phosphaturic effect of CT by indomethacin appears to be due to an inhibition of renal PG synthesis. These observations as well as our previous findings that exogenously administered PGE2 inhibits the phosphaturic effect of CT and stimulation of 1 alpha-hydroxylase in TPTX rats [Yamada et al. Endocrinology 116: 693-697, 1985] are consistent with the hypothesis that PG interacts with CT to modulate the effects of CT in the proximal renal tubules.