Recently the treatment of psoriasis with vitamin D3, its metabolites or analogues, has been reported to be clinically effective and free from side effects. We have quantified the changes in the levels of epidermal lesional keratins in 15 psoriatic patients receiving oral 1α(OH)D3 treatment. Lesions were sampled before treatment commenced and at monthly intervals for 4–6 months. Clinical resolution occurred in 7 patients within this time; 3 other patients showed incomplete lesion resolution and the remaining 5 patients showed a complete lack of response within the treatment period. Lesion resolution, as judged by clinical criteria, was accompanied by significant changes in the levels of three of the keratin polypeptides and smaller changes in others. Keratin 2 increased to levels greater than those in normal epidermis, while keratins 16 and 18 decreased to normal levels. Changes in the levels of keratins 1 and 5 were small and those of keratins 7, 10 and 14 minimal. These changes were compared with values found during lesion resolution with other therapies used in psoriasis, i.e. topical dithranol, PUVA, oral etretinate and hydroxyurea and were highly reminiscent of those observed during PUVA therapy but contrasted with those during etretinate treatment. The decrease in level of keratin 16, a hyperproliferation marker, suggests that 1α(OH)D3 inhibits keratinocyte proliferation, but at the same time the overproduction of keratin 2, a major keratin of the granular cells, indicates that there is an increase in the number of cells in the later stages of differentiation.