In guinea-pig taenia coli, cobalt ions (Co2+) inhibited the tonic response to a highly concentrated K+ solution (high-K+, 40 mM) more strongly than the phasic response. Co2+ displaced Ca2+ concentration-response curves to the right, inhibited the increase in tissue calcium content caused by high-K+, and inhibited Ca2+ binding at low affinity sites more than at high affinity sites. After treatment with Co2+, the tonic tension caused by high-K+ was not restored by a wash with normal medium, but it was restored by a wash with EDTA. The cobalt remaining in muscles was almost completely eliminated after a 20-30 min wash with EDTA. The results suggest that Co2+ binds chiefly to the surface membrane of taenia coli. Co2+ probably reduced the tension in response to high-K+ mainly by inhibiting Ca2+ influx rather than by affecting Ca2+ release.