In an attempt to elucidate the mechanism of inhibitory action of oxatomide on smooth muscle against various spasmogens, we studied the effect of this drug on cumulative dose response curves (CDRC) to CaCl2 in guinea pig ileum. We found that oxatomide induces a shift to right and a non-surmountable depression of the maximal response of these CDRC which suggests non-competitive antagonism. Furthermore, oxatomide inhibits 45Ca2+ uptake by guinea pig ileum after acetylcholine stimulation which constitutes strong evidence that inhibition of calcium ion utilization by smooth muscle cells plays a major role in the mode of action of oxatomide.