Topical application of calcitriol or its analogs is a new approach for treating psoriasis, but may be limited by systemic calcitropic effects. Calcipotriol (MC 903) is a novel calcitriol analog with low calcitropic potency after systemic application. To compare the topical potency of calcitriol and calcipotriol we applied the two drugs on the right flanks of hairless rats for 10 days. In concentrations of 0.001-0.01 g/100 ml (ethanol) the two drugs are equally effective in inducing changes in the horny layer of the skin (increase in the amount of horny material that is able to be desquamated). This can be interpreted as a stimulation of terminal keratinocyte differentiation. However, only calcitriol caused a significant rise in the serum calcium concentration. In conclusion, calcitriol and calcipotriol seem to be equally effective after topical application on the skin of hairless rats, but calcipotriol has a much lower systemic calcium liability.