We report results of experiments demonstrating a dose-dependent inhibition of spontaneous maturation (resumption of meiosis) in rat oocyte-cumulus complexes by atrial natriuretic peptide (ANP). The inhibition was persistent over the time period studied. The ANP analog Tyr8-ANP, which mediates smooth muscle relaxation in other organs without elevating cGMP levels, did not inhibit the spontaneous maturation. ANP, but not Tyr8-ANP, dose-dependently stimulated cGMP accumulation in oocyte-cumulus complexes. Furthermore, sodium nitroprusside (SNP), that stimulates a soluble form of guanylate cyclase, inhibited spontaneous maturation in oocyte-cumulus complexes and stimulated cGMP accumulation in oocyte-cumulus complexes. Neither ANP nor SNP stimulated cAMP accumulation. In oocytes where the surrounding cumulus cells had been removed neither ANP nor SNP inhibited the spontaneous maturation. These results demonstrate that cumulus cells, but not the oocyte itself, have ANP receptors and guanylate cyclases. Furthermore, ANP, via cGMP, can influence oocyte meiosis, suggesting a possible involvement of ANP and cGMP in the control of the meiotic process in rat oocytes.