OBJECTIVE The authors determined the effect of topically applied substance P (SP) on the rate of corneal epithelial wound closure in the rabbit. METHODS Uniform circular lesions, 6.5 mm in diameter, were made bilaterally in the corneal epithelium of 24 rabbits using N-heptanol. Substance P was applied repeatedly to one eye, and the SP1-7 fragment was applied to the contralateral (control) eye until wound closure was obtained. Three concentrations of peptide solution (5 x 10(-5) M, 5 x 10(-4) M, and 5 x 10(-3) M) were tested in separate groups of eight animals each. An additional eight animals received topical applications (5 x 10(-7) M) of the neurokinin-1 (NK1)-specific SP receptor antagonist CP-99,994-01 or its ineffective enantiomer CP-100,263-01. The mean rates of wound healing for each group of experimental and control eyes were determined by linear regression and analyzed by analysis of variance. RESULTS There were no statistically significant differences in the mean rates of wound closure (range, 0.083 to 0.106 mm/hour) between experimental- and control-treated corneas for any of the four groups tested. CONCLUSIONS The topical application of SP or its NK1 receptor antagonist has no significant effect on the rate of corneal epithelial wound closure in the rabbit.