The aim of this study was to further investigate the relaxation mechanism of tetrandrine (Tet), a bis-benzylisoquinoline alkaloid isolated from the Chinese medicinal herb-root of Stephania tetrandra S Moore, on rabbit corpus cavernosum tissue in vitro. The effects of Tet on the concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in isolated and incubated rabbit corpus cavernosum tissue were recorded by means of 125I radioimmunoassay. The basal concentration of cAMP in corpus cavernosum tissue was 5.67 +/- 0.97 pmol mg-1. Tet increased the cAMP concentration in a dose-dependent manner (p 0.05), but this effect was not inhibited by an adenylate cyclase inhibitor (cis-N-(2-phenylcyclopentyl)azacyclotridec-1-en-2-amine, MDL-12, 330A) (p 0.05). The accumulation of cAMP induced by prostaglandin E1 (PGE1, a stimulator of cAMP production) was also augmented by Tet in a dose-dependent manner (p 0.05). The basal concentration of cGMP in corpus cavernosum tissue is 0.44 +/- 0.09 pmol mg-1. Tet did not affect this concentration of cGMP, neither in the presence nor the absence of a guanyl cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, ODQ) (p 0.05). Further, sodium nitroprusside (SNP, a stimulator of cGMP production)-induced cGMP production was not enhanced by Tet (p 0.05). Tet, with its relaxation mechanism, can enhance the concentration of cAMP in rabbit corpus cavernosum tissue, probably by inhibiting PDEs activity.