To evaluate the toxicity of irritant chemicals on animal skin, investigators have frequently had to apply high concentrations, owing to the fact that its susceptibility is less than that of human skin. High concentrations are so damaging to tissue that specific effects are obscured on the various layers. The aim of the present study was to elucidate the effects of a variety of irritating chemicals on the skin of hairless guinea pigs. Graded concentrations of these irritating substances were applied to the back for varying periods. Histologic changes were analyzed by light and electron microscopy. The structural alterations varied greatly among the chemicals, reflecting quite different mechanisms of action. Hairless guinea pigs are quite susceptible to chemical injury, especially to their hair follicles and dermal components. The hairless guinea pig appears to be an advantageous model to assess the acute and chronic effects of chemical irritants.