In the guinea-pig stomach fundus strips, set in cascade, amrinone (3 microM to 0.3 mM) induced contractions which were followed by relaxation only at the highest amrinone concentrations tested (30 mM to 0.3 M). Contractions were transient and scarcely related to the drug concentration used, whereas relaxation was the most pronounced and concentration-dependent effect. The transient contraction elicited by amrinone was abolished by scopolamine, indicating activation of cholinergic receptors, but it was unaffected by low temperature or hemicholinium-3. The relaxing effect induced by amrinone was unaffected by low temperature, by the receptor inhibitors used (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine) and by indomethacin. It was potentiated by dipyridamole (0.1 microM) and completely suppressed by tissue pretreatment with adenosine deaminase (10 U/ml). Inhibition of this effect was also obtained by reducing Ca2+ concentration in the perfusion fluid or by pretreating the preparations with verapamil. These results indicate the involvement of endogenous adenosine in the relaxing effect of amrinone and the requirement of Ca2+ influx through plasma membrane for this effect.