The diterpenes previously isolated from the leaves of Croton zambesicus were tested to evaluate their vasorelaxant activity on the Wistar rat aorta. Their vasorelaxant effect was compared to a series of synthetic trachylobanes and related polycyclic compounds on KCl- or noradrenaline-induced contractions in order to evaluate structure-activity relationships. We demonstrate the vasorelaxant properties of some pure trachylobane diterpenes at low concentration (IC50 < 10 microM) on KCl-induced contractions, but none have a significant effect in noradrenaline-induced contractions. Comparing structures and activity we observed that a C-14 carbonyl group associated with a C-15 hydroxy or ketone function or a C-3 carbonyl associated with a hydroxymethyl group plays an important role in the vasorelaxant activity of trachylobane diterpenes. We also observed that the absolute configuration or the cleavage of the C13-C16 cyclopropane bond does not have a marked effect on the activity. The cytotoxicity of all of these compounds has also been evaluated on HeLa cells in order to verify that the vasorelaxant activity was not correlated with general cytotoxicity.