We have studied the effect of nitric oxide (NO) on the production of arachidonic acid ([14C]-AA) metabolites in the rat oviduct. The basal synthesis of eicosanoids was measured by the conversion of ([14C]-AA) to the different radiolabeled products of cyclooxygenase (COX). The oviducts incubated for 1 h with the labeled substrate of COX were able to convert 3.3 +/- 0.3% of ([14C]-AA) to 6-ceto-PGF1alpha, 10.7 +/- 1.0% to PGF2alpha, 13.5 +/- 1.2% to PGE2 and 6.3 +/- 0.5% to TXB2. The tissues were incubated with different doses of two NO donors: SIN-1 and Spermine NONOate. The results indicated that SIN-1 produces a significant decrease (50%; P < 0.05) in all prostanoids evaluated in a dose-response fashion. The inhibitory effect was completely reversed by addition of 20 microg/ml of hemoglobin (Hb), a NO scavenger. The addition of Spermine NONOate to the incubation medium diminished significantly (65%) the synthesis of COX metabolites suggesting that NO acts by inhibiting COX activity in the rat oviduct. However, NOS inhibitors, N(G)-L-arginine-methyl-ester (L-NAME) nd N(G)-L-monomethyl-arginine (L-NMMA) had no effect on basal production of the prostanoids. These results indicate that in the rat oviduct the synthesis of COX metabolites is negatively regulated by nitric oxide.