We investigated the vasodilating effects of verapamil, nifedipine, and nitroglycerin in relation to plasma levels of 6-keto-prostaglandin (PG)-F1 alpha, PG E1, PG F2 alpha, and thromboxane (TX) B2 in dogs. Verapamil, nifedipine, and nitroglycerin decreased peripheral vascular resistance from 1.00 +/- 0.07 mmHg/ml/min (mean +/- SE) to 0.83 +/- 0.05, from 0.99 +/- 0.06 to 0.80 +/- 0.05, and from 1.03 +/- 0.04 to 0.91 +/- 0.04, respectively. However, peripheral blood flow did not change significantly. Administration of verapamil significantly increased plasma levels of 6-keto-PG F1 alpha, PG E1, and PG F2 alpha from 150 +/- 31 pg/ml to 350 +/- 98, from 56 +/- 34 to 87 +/- 33, and from 127 +/- 35 to 238 +/- 61, respectively, while neither nifedipine nor nitroglycerin had any effect on plasma 6-keto-PG F1 alpha, PG E1, and PG F2 alpha. Indomethacin pretreatment reduced the effects of verapamil on peripheral vascular resistance and plasma PG concentration. None of these drugs caused a significant change in the plasma TX B2 level. The results suggest that the vasodilating action of verapamil was mediated in part by the prostaglandin system.