Normal subjects and ichthyotic patients were biopsied before and after etretinate (Tigason) therapy. Histometric and cell kinetic measurements showed minimal changes following treatment. The metabolic activity across the epidermis was measured by a novel approach using the Quantimet 720 image analyser, and was significantly increased in the normal subjects as demonstrated by glucose-6-phosphate dehydrogenase (G6PDH), succinic dehydrogenase (SDH) and non-specific esterase (NSE) activities. In the ichthyotics studied the levels of G6PDH and SDH activity were significantly lowered following etretinate therapy, to levels similar to those demonstrated in normal subjects. In contrast, the activity of NSE was increased in the ichthyotics after etretinate therapy. It is suggested that the effect of retinoids is to 'normalize' the process of epidermal differentiation when it is abnormal.