The effects of thiamylal and pentobarbital on contractions mediated through the influx of extracellular Ca(++) and the release of intracellularly stored Ca(++) were compared in rat aortic strips. Thiamylal (3 x 10(-5) M to 10(-3) M) and pentobarbital (10(-4) to 10(-3) M) significantly attenuated the contraction induced by KCl (20 mM), and shifted the dose-response curve for Ca(++) of KCl (20 mM)-treated strips downwards and to the right. Caffeine (10(-2) M)-induced contraction was significantly attenuated by thiamylal at concentrations greater than 10(-4) M and by pentobarbital at 3 x 10(-4) M. Only a high concentration (10(-3) M) of these barbiturates significantly inhibited the contractions induced by norepinephrine (NE, 10(-6) M) in Ca(++)-free medium. Contraction of strips without endothelium by a Ca(++) ionophore, A23187 (5 x 10(-6) M), in the presence of a Ca channel blocker, was relaxed by high concentrations of thiamylal (3 x 10(-4) M to 10(-3) M) and pentobarbital (10(-3) M). It is concluded that thiamylal inhibits contraction through an intracellular action as well as a Ca channel-blocking action in vascular smooth muscle of rat aorta. However, the intracellular action of pentobarbital is less potent than that of thiamylal.