The application of bradykinin or capsaicin to the rabbit eye evoked strong miosis. The effect could be prevented by pretreatment of the eye with tetrodotoxin (TTX) or a substance P (SP) antagonist. However, the miotic response could be elicited despite TTX or the SP antagonist if the dose of capsaicin or bradykinin was increased. Bradykinin and capsaicin contracted the isolated rabbit sphincter pupillae muscle. The contraction produced by bradykinin and capsaicin was unaffected by TTX but reduced by specific SP antagonists. This indicates that bradykinin and capsaicin exert their effects on the isolated sphincter muscle through the release of SP but independent of neuronal conduction. In vivo, the situation seems to be different. The finding that TTX is capable of blocking the miotic response to moderate doses of bradykinin and capsaicin suggests that the effect on the eye under these circumstances is dependent upon a normal impulse traffic.