Effect of zinc sulphate was studied on histamine-induced contractions on guinea-pig ileum. In doses of 1.72 X 10(-7)M or less no effects were observed. Zinc sulphate in doses of 3.44 X 10(-7)M, 6.88 X 10(-7)M and 1.72 X 10(-6)M produced dual effect. Short exposure of tissue for 10 min to zinc sulphate resulted in significant dose dependent potentiation of histamine effect whereas after washing the tissue of zinc sulphate, histamine response was inhibited significantly and in a dose dependent manner. Higher concentrations of zinc sulphate of 3.44 X 10(-6)M and above produced irreversible inhibition of histamine response. The above observations have been explained in terms of zinc-calcium interaction. It is hypothesized that interaction of zinc with calcium may take place extracellularly at membrane level and intracellularly.