The purpose of our study was to examine the relaxant effects of sodium nitroprusside (SNP) and cyclic guanosine 3'-5'-monophosphate (cGMP) on pregnant rat myometrium. Using very thin muscle strips, which allows diffusional access of applied drugs (in a few seconds), contractile properties were examined. This technique facilitates study of SNP's effects on uterine contractility as nitric oxide is rapidly inactivated to NO2. SNP did not decrease the amplitudes of 45 mmol/l KCl contractions but decreased spontaneous contractions and 1 mumol/l carbachol contractions. The relaxation of carbachol contractions by SNP were antagonized by methylene blue. In addition, 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) also inhibited KCl-, carbachol- and oxytocin-induced contractions, however, the relaxant effect of 8-bromo-cGMP was much greater on carbachol and oxytocin contractions than on KCl contractions. Cyclic GMP (1 microM) decreased contractions evoked by various concentrations of Ca2+ and carbachol with 1 mumol/l GTP-gamma S in skinned (membrane-permeable) strips. These results demonstrate that SNP stimulates guanylate cyclase to produce cGMP and that the relaxant effect of cGMP was predominant on pharmaco-mechanical coupling. The cyclic-GMP system may help in maintaining pregnancy and preventing uterine contractions during exposure to stimulating agonists.