The influence of topical application of MC903, an analogue of 1 alpha,25-dihydroxyvitamin D3, on psoriatic plaques was investigated during a long-term treatment study. The parameters for epidermal growth and for inflammation were assessed on frozen sections using immunohistochemical methods to elucidate their modulations in time and the interrelations between the different cell types involved during treatment with MC903. Biopsies were taken before and after 1, 2, 4 and 12 weeks of treatment. Monoclonal antibodies against the hyperproliferation-associated keratin 16, against cycling nuclei, and against T lymphocytes, B lymphocytes, Langerhans cells and CD14-positive cells were used in combination with a polyclonal antibody against polymorphonuclear leucocyte (PMN)-elastase. The earliest change was a statistically significant decrease in PMN after 1 week of treatment followed by a decline of cycling nuclei after 2 weeks. These changes preceded a decrease of T lymphocytes which occurred after 4 weeks. Keratin 16 content tended to diminish after 4 weeks of treatment. CD14+ cells decreased slightly during the observation period, whereas Langerhans cells tended to increase. No B lymphocytes were found. These results suggest that MC903 influences the number of PMN and epidermal growth rather than the number of T lymphocytes.