The beneficial effect of isotretinoin on the repair of photodamaged skin is well documented. Little is known, however, on the action of this compound on immunological functions of epidermis. In a double-blind study, we analyzed the effect of topical applications of isotretinoin on human Langerhans cell (LC) function by using the mixed epidermal cell lymphocyte reaction (MELR). Isotretinoin cream (0.1%) was applied daily for 4 months on the back of one hand of 5 healthy volunteers, 50-60 years of age. The back of the other hand received vehicle alone and was used as control. Skin biopsy specimens were taken at the end of treatment. Epidermal cell (EC) suspensions were obtained by the use of trypsin and allogeneic T cells were purified from the peripheral blood of allogeneic donors. MELR was performed in microtiter plates and T cell proliferation was assessed by 3H-thymidine incorporation during the last 18 h of culture. Results did not show any differences between allogeneic T cell responses to EC from isotretinoin-treated or nontreated skin. These results therefore suggest that isotretinoin, applied topically onto photodamaged skin, did not alter human LC antigen-presenting function.