In accordance with the data reporting the identification of nitric oxide synthase (NOS) and vasoactive intestinal polypeptide (VIP) positive nerve fibres in the trabecular meshwork of the corpus cavernosum, we suggest that nitric oxide (NO) and VIP may serve complementary physiological roles in penile erection. Therefore SIN-1 and VIP were administered alone and in combination in an in vivo rabbit model. All rabbits revealed basal pressure values of 5 - 8 cm H2O intracavernously. In the rabbits intracavernously (i.e.) injected with SIN-1 alone and VIP alone, no adequate erectile responses were observed. Whereas, in the group intracavernously injected with the combination of SIN-1 + VIP, erectile responses with mean maximal intracavernous pressure (max. ICP) 52.8 (+/-13.2) cm H2O were noted. These pressure elevations do not statistically diverge (P > 0.05) than the ones obtained in the control group administered i.e. injections of the combination of papaverine/phentolamine (mean max. ICP 51 (+/-14.73) cm H2O). Referring to our results, we conclude that the combined use of SIN-1 + VIP could play an important role in the physiological treatment of erectile dysfunction.