The effect of synthetic omega-conotoxin (omega-CgTX) on the contractile responses of segments of rat ileum, stomach fundus and uterus and guinea pig taenia coli were investigated. Omega-CgTX (10(-9)-5 x 10(-6) M) did not inhibit the contractile responses of all smooth muscle segments to high KCl and/or ACh. However, unexpectedly, omega-CgTX (3 x 10(-7)-10(-5) M) alone caused dose-dependent contraction of segments of the stomach fundus and uterus. These contractile responses to omega-CgTX alone depended upon the presence and/or the influx of extracellular Ca2+; and they were inhibited by calcium antagonists such as diltiazem, nitrendipine and verapamil, with the exception that the segments of stomach fundus was not inhibited by verapamil. With the segments of uterus, but not those of other tissues, omega-CgTX (10(-7)-5 x 10(-6) M) significantly enhanced the contractile responses to various concentrations of ACh and high KCl. With rat ileum and guinea pig taenia coli segments, omega-CgTX (10(-9)-5 x 10(-6) M) did not induce a contractile response or have an enhancing effect. These findings suggest that omega-CgTX may have a calcium agonist-like effect on smooth muscles such as the stomach fundus and uterus of rats.