Recently, it has been demonstrated that the endothelium of corpus cavernosum (CC) plays an important role on smooth muscle relaxation, which is crucial to initiate and maintain erection. We investigated the effect of long-lasting additional testosterone propionate (TP) therapy on endothelium-dependent and -independent relaxations of isolated rabbit CC. Isolated CC strips were mounted in organ baths and isometric tension was recorded. Addition of a specific inhibitor of nitric oxide synthesis, N-G-nitro-L-arginin methyl ester (L-NAME), into the organ bath had no effect on the relaxation responses to adenosine (ADO), adenosine 5'-triphosphate (ATP) and sodium nitroprusside (SNP) in isolated CC strips precontracted with phenylepherine, but completely inhibited relaxation responses produced by ADP. Adenosine and adenine nucleotides relaxed the phenylepherine-induced contractile response in control strips with the potency order: ADO (62.8 +/- 3.2%) > ATP (37.1 +/- 5.2%) > ADP (25.8 +/- 2.5%). The relaxation responses to ADO, ATP and SNP in isolated rabbit CC strips were not significantly altered by additional TP therapy. The relaxation responses produced by ADP were significantly enhanced following 1 and 2 months TP therapy as compared with controls. However, in the group treated with TP for 2 months followed by a 2 months drug-free period, relaxation responses were significantly reduced compared to 1 and 2 months treatment groups, and approached control values. Increased relaxation responses to ADP following 1 and 2 months additional TP therapy may be a result of increased endothelial purinergic receptor density, or it may be due to stimulation of the synthesis and/or release of endothelial nitric oxide (NO) by TP. (C) 1998 The Italian Pharmacological Society.