In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2 alpha (PGF2 alpha), the addition of pentobarbital (10(-5) to 10(-3) mol.l-1) caused dose-related relaxation, whereas thiamylal and thiopental in a low concentration (10(-5) to 10(-4) mol.l-1) caused further contraction and in a high concentration (10(-3) mol.l-1) profound relaxation. Thiobarbiturate-induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2 alpha. In cerebral and mesenteric arteries exposed to Ca(++)-free media for 60 min and treated with KCl or PGF2 alpha, reintroduction of Ca++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca(++)-induced persistent contraction was attenuated by pretreatment with pentobarbital (10(-4) to 10(-3) mol.l-1) and thiamylal (10(-3) mol.l-1); the attenuation was greater in arteries treated with KCl than with PGF2 alpha. The Ca(++)-induced contractions of mesenteric artery treated with PGF2 alpha were potentiated by 10(-4) mol.l-1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl-induced depolarization than by a stimulation of PGF2 alpha receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor-operated Ca++ channel for PGF2 alpha.