The effects of 2-[p-(dimethylamino) styryl]pyridine methiodide (DSPM) on rabbit aortic contraction induced by high K+, norepinephrine (NE) and Ca2+ were studied. On rabbit thoracic aortic strips, DSPM inhibited the contraction induced by KCl and NE in normal modified Tyrode's solution. DSPM shifted the dose-response relationships of KCl and NE to the right, and depressed their maximal responses; the pD'2 values were 5.09 and 5.16 respectively. After the strip had been exposed to Ca2(+)-free Tyrode's solution for 2 h, the NE-induced responses were further inhibited by DSPM, whereas the KCl-induced responses were not significantly affected. On depolarized vessels, the dose-response relationships of CaCl2 were also shifted to the right and their maximal responses were also depressed by DSPM, suggesting that DSPM is a non-competitive antagonist. The pD'2 value was 6.86. These results suggest that DSPM is a calcium antagonist. It not only inhibited the influx of extracellular calcium, but also has an inhibitory effect on the release of sequestered calcium in the rabbit aortic smooth muscle.