We studied the effect of tacalcitol (1 alpha, 24 dihydroxy vitamin D3) ointment on clinical and immunohistochemical efficacy in psoriatic patients during 2 months of treatment. The psoriasis area and severity index decreased significantly after only 1 month and the total body surface index decreased 55% after 2 months. To characterize the epidermal compartment keratin 14, keratin 16, epidermal growth factor receptor, apoptotic and Ki-67 positive cells were examined. After 1 week of treatment no significant changes were found in any of these parameters. After 2 months, keratin 16 reached the levels observed in normal skin and Ki-67 and keratin 14 expression also reduced significantly. Epidermal growth factor receptor staining and the number of apoptotic cells did not alter during treatment. We conclude that tacalcitol is effective in the treatment of plaque psoriasis. Because the main epidermal effect observed immunohistochemically is a reduction in proliferation, a combination therapy using either corticosteroids, vitamin A derivatives or dithranol seems rational.