The aim of this study was to clarify the possible involvement of nitric oxide (NO) on prostaglandin (PG) E 2-9-ketoreductase activity in the gonadotropin-releasing hormone (GnRH)-dependent PGF 2α synthesis by the interrenal gland of the female water frog, Rana esculenta, during the post-reproduction. Interrenal glands were incubated in vitro with GnRH, NO donor (sodium nitroprusside, SNP), and inhibitors of phospholipase C (compound 48/80), inositol triphosphate (decavanadate), calmodulin (calmidazolium), NO synthase ( L-NAME), and PGE 2-9-ketoreductase (palmitic acid). Production of PGE 2 and PGF 2α and NO synthase and PGE 2-9-ketoreductase activities were determined. GnRH and SNP increased PGF 2α production and PGE 2-9-ketoreductase activity, and decreased production of PGE 2 and GnRH increased NO synthase activity. GnRH effects were blocked by all inhibitors, except for palmitic acid, which did not affect NO synthase activity, which is increased by GnRH. This study indicates that NO may be involved in regulation of the R. esculenta post-reproduction through stimulation of PGE 2-9-ketoreductase activity in GnRH-dependent PGF 2α synthesis by the frog interrenal gland.