It is well known that phosphodiesterase inhibitors, such as MB 22948 or papaverine, induce endothelium-dependent relaxation by potentiating the effects of endothelium-derived relaxing factor released spontaneously in vascular tissues. The present study was planned to determine whether the vasodilator properties of pentoxifylline, a phosphodiesterase inhibitor, are endothelium-dependent and modulated by its phosphodiesterase inhibitory activity in rabbit aorta. In opened aortic rings precontracted with phenylephrine (0.5 microM), pentoxifylline (1 microM-1 microM) caused concentration-dependent relaxation. Pentoxifyl line-induced relaxation was not modified by incubation with methylene blue (10 microM) or NG-nitro-L-arginine methyl ester (0.1 microM), or by mechanical denudation of endothelium. Forskolin (1nM-0. 1mM) and sodium nitroprusside (10nM-0. 1mM) induced concentration-dependent relaxations in both endothelium containing and endothelium denuded preparations. The relaxation induced by forskolin and sodium nitroprusside, which are cyclic AMP and cyclic GMP mediated, respectively, and which are both endothelium-independent, were not altered after incubation with pentoxifylline (0.1 mM) for 30 min. In conclusion, our experiments suggest that the vasodilator properties of pentoxifylline in isolated rabbit aorta are primarily at the level of the vascular smooth muscle and may not involve EDRF or its phosphodiesterase inhibitory activity.