Rat skin was treated with 35 mM-sodium lauryl sulphate (SLS) and samples were taken after one, three or five treatments, or 24 hr after the fifth treatment for measurement of enzyme release and epidermal enzyme levels. Release of acid phosphatase (AP) and lactate dehydrogenase (LDH) was significantly higher than in controls after five treatments with SLS, and epidermal levels of AP, LDH and N-acetylglucosaminidase were also higher than in controls in skin taken 24 hr after the fifth treatment. The relationship of these changes to the irritant response, assessed visually and histologically, was investigated in two out of three experiments. Although the timing of the irritant response was variable, enzyme release accompanied the development of erythema and oedema in each case, and extensive enzyme release was associated histologically with epidermal oedema and an increase in dermal leucocytes. The increase in epidermal enzyme activities also followed the development of the reaction to SLS, and it seemed to be related to epidermal thickening.