Bencyclane (N-[3-(1-benzyl-cycloheptyloxy)-propyl]-N,N-dimethyl-amine-hydrogenfumarate, Fludilat), inhibits phosphodiesterase(PDE)-activity in vitro similarly to several other smooth muscle relaxants. Compared with papaverine this inhibitory effect of bencyclane on PDE is weak despite of its strong relaxant effect on smooth muscle, which is about equal to that of papaverine. 14C-Bencyclane is accumulated 8-fold in the smooth muscle tissue of bovine coronary arteries, indicating that relaxation is caused by 8-fold higher concentrations in the tissue than in the organ bath. A comparison of (corrected) ED50-values for relaxation with Ki-values for PDE-inhibition obtained with several PDE-inhibitors, including bencyclane, yields a significant correlation between both parameters. Since in subsequent studies in isolated tracheal muscle strips bencyclane at maximum relaxing concentrations did not increase cAMP, which was in contrast to the actions of papaverine or aminophylline, it is likely that bencyclane-induced smooth muscle relaxation is unrelated to inhibition of PDE or cAMP. In the same dose range in which bencyclane relaxes smooth muscles it exerts a non-specific antiadrenergic inhibitory effect, possibly due to its local anesthetic action at the cell membrane. It is also possible that the myocardial inhibitory effect of bencyclane is caused by a direct Ca++-antagonistic mechanism (Fleckenstein et al. 1971).