The vasodilation mechanism induced by ketamine was investigated in isolated smooth muscle strips of rabbit portal veins. Ketamine inhibited both the phasic and tonic components of K(+)-induced contraction at concentrations greater than 500 microM and 100 microM, respectively. This effect was reversible and concentration-dependent with concentration-dependent with concentrations up to 1 mM. These effects were similar to those produced by verapamil. In the presence of 60 mM K+, application of Ca2+ (2.5 mM) in the perfusing solution caused tonic contraction of the smooth muscle, and ketamine at concentrations larger than 10 microM strongly inhibited this Ca(2+)-induced contraction. Ketamine (100 microM) also inhibited the K(+)-induced contractions significantly in the absence and presence of guanethidine, tetrodotoxin and propranolol. Ketamine produced similar concentration-dependent relaxations in the tissues with and without endothelium. These results indicate that in rabbit portal vein, vasodilation produced by ketamine is not endothelium-dependent but is likely to be due to blockade of the voltage-gated influx of extracellular Ca2+.