OBJECTIVE To determine if androgens directly regulate veno-occlusion or if androgens act indirectly to maintain the penile structures which control outflow. METHODS Using CASTRATE and TESTO rats, measurement was made of mean arterial pressure (MAP), intracavernosal pressure (CCP), and intracavernosal flow (CCF) during erection resulting from stimulation of the autonomic innervation of the penis. CCP and CCF were also measured during saline infusion into the cavernosal sinuses before and after treatment with sodium nitroprusside (SNP, a nitric oxide donor drug) to fully relax cavernosal smooth muscle. Penile tissue was also collected to measure the content of alpha actin and proline and hydroxyproline to determine if brief withdrawal of androgenic support led to changes in the number of smooth muscle cells or the collagen content of the tissue. RESULTS Infusion of saline into the cavernosal sinuses demonstrated that veno-occlusion was defective in CASTRATE rats while veno-occlusion was fully functional in TESTO animals. Furthermore, veno-occlusion could be induced in CASTRATE rats if they were first treated with SNP. This observation suggests that failure of veno-occlusion in the CASTRATE rats is due to a deficiency in the production of NO resulting in a reduction in the degree of relaxation of the penile smooth muscle. The measurements of smooth muscle a actin and proline and hydroxyproline content of collagen showed that both were unaffected by castration and that the basic structure of the penis did not degenerate after one week without androgenic support. CONCLUSIONS These results can be interpreted to mean that androgens control the veno-occlusive mechanism indirectly via a NO dependent mechanism and not by maintaining the structures of the penis which are essential to veno-occlusion.