Immunocytochemical techniques using antibodies to the specific T6 and Ia (Major Histocompatibility Complex, class II, human HLA-Dr) antigens were used to determine the densities of epidermal Langerhans cells (LC) in psoriasis patients treated with the aromatic retinoid RO 10-9359. Fourteen patients were treated with the aromatic retinoid and were skin biopsied before, during and after therapy. Two psoriasis patients receiving PUVA (systemic 8-methoxypsoralen + UVA irradiation) were included in the study. The results showed an increase in LC numbers during aromatic retinoid administration, which coincided with an improvement in the clinical severity of the lesions. At the end of retinoid administration the LC numbers were similar to those found in the initial psoriatic plaques. The density of Ia+ LC, in comparison with T6+ LC in the epidermis of psoriatic plaques were significantly different. Dendritic and non-dendritic Ia+ cells were also observed in the dermis of the plaques. Unlike aromatic retinoid treated patients, PUVA treated patients showed a decrease of both T6+ and Ia+ epidermal LC by the middle of therapy, a total absence of immunoreaction by the end of therapy, and a return to normal skin values a few weeks after treatment. This immunocytochemical study helps in distinguishing between dendritic and other possible Ia-expressing cells from the infiltrate that may penetrate the epithelium. These results do not conclusively demonstrate the role of LC in the pathogenesis of psoriasis. Other factors, such as the interrelationship with other immune response cell types and alterations in the lymphokine cascade may be important.