The effects of L-arginine, the precursor in the synthesis of nitric oxide (NO), were investigated in the penile bulb isolated from saline (control) or lipopolysaccharide (20 mg/kg, i.p.)-treated rats. Four consecutive concentration-response curves for L-arginine were made at hourly intervals with the penile bulb. L-arginine (10(7) - 10(-3) M) elicited a concentration- and time-dependent relaxation response in the control group. The NO synthase (NOS) inhibitors, N-G-methyl-L-arginine (L-NMMA) and aminoguanidine, guanylate cyclase inhibitor, 1-H[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) and protein synthesis inhibitor, cycloheximide, inhibited L-arginine-induced relaxation. In the lipopolysaccharide-group, L-arginine produced a pronounced non-time-dependent relaxation at the first concentration-response curve, which was not different from the fourth response of the control group. This response was also inhibited by aminoguanidine. These results show that L-arginine induced NO-mediated relaxation and suggest the presence of a biochemical pathway converting L-arginine to NO, which is probably an inducible type in the penile bulb. (C) 2002 Elsevier Science B.V. All rights reserved.