OBJECTIVE To investigate smooth muscle responsiveness in isolated preparations of corpus cavernosum from men with vasculogenic impotence. METHODS Biopsies of corpus cavernosum were obtained from 63 men undergoing penile surgery. These included a control group of eight men (mean age 59 years, range 38-82) undergoing penile amputation for carcinoma, 47 men with vasculogenic impotence (mean age 58, range 36-72) who were further sub-divided into arterial (n = 9), venous (n = 24) or mixed arterial/venous (n = 14) impotence according to the results of pre-operative haemodynamic investigation, and eight men with non-vasculogenic impotence (mean age 49 years, range 34-66). Smooth muscle contractile responses to alpha-adrenoceptor activation and relaxant responses to stimulation of intrinsic nerves and exposure to papaverine and sodium nitroprusside were recorded in tissue strips prepared from the biopsies. Morphology was assessed histologically using haematoxylin and eosin staining of tissue sections together with immunocytochemical labelling of intrinsic nerves. RESULTS Nerve-evoked relaxation was markedly impaired in tissue from men with venous or mixed arterial/venous impotence. A lesser degree of impairment was found in tissue from men with arterial impotence alone. Tissue from men with all types of vasculogenic impotence also showed a decreased contractile response to alpha-adrenoceptor stimulation. The magnitude of relaxant responses to papaverine and sodium nitroprusside in the vasculogenic group was similar to that of the control. There were no differences in smooth muscle content or nerve density between the vasculogenic group and the control. In the non-vasculogenic group responses to relaxant nerve stimulation, alpha-adrenoceptor activation and relaxant drugs were similar to those of the control. Nerve density in this group was similar to the control but smooth muscle content was reduced. CONCLUSIONS The results of this study demonstrate a functional impairment of smooth muscle contractility and neurogenic relaxation in corpus cavernosum from impotent men with abnormal penile haemodynamics. Altered smooth muscle responsiveness is likely to be a factor in the aetiology of impotence in such men and may contribute to the relatively poor results of vascular surgery for impotence.