The diffusion, penetration, and surface effects of benzocaine incorporated in various polyethylene glycol ointment bases through human stratum corneum were studied. Benzocaine diffusion was measured by following the benzocaine concentration in the receiving compartment of a diffusion cell. The ointment was placed in the other cell compartment and was separated from the receiving compartment by sheets of human stratum corneum. Surface effects were monitored by scanning electron micrographs of the stratum corneum. Results showed a decrease in drug diffusion in the presence of relatively high amounts of the lower molecular weight portions of polyethylene glycol. Scanning electron microscope studies showed that both benzocaine and polyethylene glycol affect the surface structure of the stratum corneum. Thermal analysis indicated that benzocaine dissolves in polyethylene glycol.