We examined whether prostacyclin (PGI2), a prostaglandin synthesized in the renal cortex that increases adenosine 3',5'-cyclic monophosphate levels in distal nephron epithelia, mediates increased HCO3 secretion in in vivo perfused distal tubules of anesthetized rats given dietary HCO3. Animals eating a minimum electrolyte diet given 80 mM NaHCO3 drinking solution increased urine excretion of 6-keto-PGF1 alpha, a PGI2 metabolite, by 2.6 +/- 0.3-fold compared with those drinking distilled H2O. NaHCO3 animals infused with indomethacin to inhibit PGI2 synthesis had lower HCO3 secretion than those without indomethacin (-8.9 +/- 0.9 vs. -18.7 +/- 1.8 pmol.mm-1.min-1, P < 0.01). By contrast, NaHCO3 animals infused with both PGI2 and indomethacin had higher HCO3 secretion than those given indomethacin alone (-16.0 +/- 1.5, P < 0.02 vs. indomethacin group). HCO3 secretion was not different between controls with and without indomethacin but was higher in the PGI2 + indomethacin compared with the indomethacin alone controls (-11.2 +/- 1.2 vs. -4.5 +/- 0.5, P < 0.01). The data show that PGI2 increases distal tubule HCO3 secretion in rats and suggest that this agent contributes to the increased distal tubule HCO3 secretion induced by dietary HCO3.