Papaverine is believed to relax smooth muscle by reducing transmembrane calcium transport and cyclic nucleotide phosphodiesterase activity. The present study characterizes the different relaxing effects of papaverine on isolated muscle strips of rat bladder dome. Compared to histamine, norepinephrine and serotonin, carbachol and high potassium induced the most prominent contractions in rat bladder strips. For this reason both agents were used as stimulants. High-potassium-induced muscle contractions were reduced by a lower concentration of papaverine than carbachol-induced muscle concentrations. Compared to verapamil, papaverine, especially in low concentrations, was less potent on both kinds of induced muscle contractions. These tension responses correspond to a difference in 45Ca uptake, suggesting a nonspecific blocking property of papaverine on transmembrane calcium channels. The beta-sympathomimetic effects of isoprenaline on carbachol-induced contractions were not enhanced by verapamil. In contrast, papaverine increased this tension response of isoprenaline on carbachol-induced contraction. From these results it is possible that part of the papaverine action seems to be related to an intracellular mechanism probably to cAMP.