Endothelin-1 (0.5-10 nM) produced a concentration-related contraction of the isolated iris sphincter muscle. The contraction rate of the muscle was slower for endothelin than carbachol, but endothelin was also more potent than carbachol, although the maximum contraction size was greater for carbachol. The endothelin response was unaffected by atropine whereas the carbachol effect was abolished. Endothelin-1 and carbachol stimulate the accumulation of inositol phosphates in a concentrationrelated way. The endothelin response was unaffected by atropine, prazosin or ketanserin, but the carbachol effect was specifically-antagonized by atropine. It is suggested that activation of endothelin-1 receptors to stimulate phosphatidylinositol hydrolysis may be the initial phase in the contraction response of the iris sphincter muscle.