The effects of ATP, ADP, AMP and adenosine were studied on the spontaneous mechanical activity of the rat portal vein. 2It was found that STP and ADP, in concentrations higher than 300 mug M, caused a transient tetanus, followed by inhibition, and at lower concentrations an increase in the frequency and amplitude of the spontaneous contractions. AMP and adeosine on the other hand, inhibited spontaneous activity, by reducing the amplitude of contractions and increasing their frequency. The effects were dose-dependent. ATP was found to be 2.2 times more potent than ADP, while AMP and adenosine were equipotent. Weak inhibitory effects were obtained with GMP, guanosine and adenine, while GTP, 3K-cyclic AMP and guanine had no effect. ATP and ADP increased the K-contracture, while AMP and adenosine relaxed it. The effects of ATP were augmented in Mg-free solutions and partially inhibited in Mg-high solutions in the normally polarized muscle, while Mg had no influence on the ATP-induced contraction in the depolarized muscle. Theophylline potentiated the inhibitory response to AMP and adenosine. Adrenergic and cholinergic blockers had no influence on the response to ATP, ADP, AMP or adenosine. It is suggested that the effects of ATP and ADP are linked with Ca++ movements across the membrane, while AMP and adenosine might stimulate intracellular metabolism causing increased intracellular Cs-++ binding.