Severe ototoxicity has been observed in laboratory rodents after middle ear application of ototopical preparations or their constituents. Owing to their relatively high susceptibility, these animals may not be ideal experimental models. In the present study the ototoxicity of Cortisporin Otic Suspension (neomycin, polymyxin B, hydrocortisone) was studied using the baboon as a primate model. Middle and inner ear pathologic changes were assessed after a single application of the suspension to the tympanic cavity. Inner and outer hair cell loss occurred in all the experimental animals; it was, however, confined to the basal turn of the organ of Corti. Relative to previously studied rodents, the thicker, more densely structured round window membrane of the primate appears to provide better protection against penetration of ototoxic agents. Nonetheless, the results of this study indicate that ototopical preparations must be used with caution in clinical situations in which they may reach the middle ear.