The present study investigated the role of hippocampal nitric oxide (NO) in memory retention of an inhibitory avoidance learning task in rats. The anatomical locus was aimed at the dentate gyrus (DG). Results indicated that intra-DG administration of a NO generator, sodium nitroprusside (SNP), at moderate doses enhanced retention performance in a dose-response fashion in rats. SNP at higher doses, on the other hand, impaired memory retention. Intra-DG injection of a NO inhibitor, L-NG-monomethylarginine (L-MeArg), impaired retention performance at moderate doses. Coadministration of a NO precursor L-arginine (2.9 and 7.2 micrograms) reversed the memory-impairing effect of L-MeArg. An in vitro ADP-ribosylation experiment showed five protein bands with molecular weights around 118, 94, 54, 43, and 39 kDa that were labeled. The labeling intensity of these proteins decreased as the concentration of in vivo SNP increased. These results suggest that hippocampal NO plays a facilitatory role in the memory process of an inhibitory avoidance learning task in rats.