PURPOSE: Estrogen relaxes vascular smooth muscle via genomic and non-genomic mechanisms. Most studies of the role of estrogen in the relaxation response have been conducted in females, and little information is available in males. This study investigated whether estrogen plays a role in relaxation of the rabbit cavernous smooth muscle. MATERIALS AND METHODS: Relaxation responses of rabbit cavernous smooth muscle to estrogen (30 nM, 300 nM, 3 micrometer, 30 micrometer) were observed in vitro. The responses of the muscle strips to estrogen after incubation with the transcription inhibitor dactinomycin (10 micrometer) or the nonspecific nitric oxide (NO) synthase inhibitor L-NAME (10 micrometer) also were evaluated. RESULTS: Estrogen caused dose-dependent relaxation of strips contracted by norepinephrine. The maximal response was seen about 10 minutes after treatment. Estrogen-induced relaxation was not prevented by dactinomycin or L-NAME, suggesting that the response was not mediated by gene transcription or NO. CONCLUSIONS: Estrogen may be involved in relaxation of rabbit cavernous smooth muscle via a non-genomic NO-independent mechanism.