Effects of substance P on the isolated iris sphincter muscle of the albino rabbit were studied. The muscle was incubated in an organ bath containing Krebs' physiologic solution and the muscle tension was recorded with an isometric transducer. Substance P induced dose-dependent muscle contraction in the concentration range from 3 x 10(-11) to 3 x 10(-7) M and ED50 was estimated to be 3.7 x 10(-9) M. The muscle contraction was not antagonized by tropicamide, phentolamine, propranolol, chlorpheniramine, cimetidine, methysergide or baclofen. Tetrodotoxin (3 x 10(-7) g/ml) pretreatment did not change the muscle contraction induced by substance P. A retrobulbar capsaicin injection did not cause supersensitivity in the muscle response to substance P. These results indicate that the iris sphincter muscle contraction caused by substance P is not mediated by cholinergic-, adrenergic-, histamine- or serotonine-recepters and suggests that its action on the muscle is direct.