The therapeutic efficacy and local and systemic safety of 3μg/g calcitriol ointment twice daily was assessed in a randomized, double-blind, vehicle-controlled, left-right study for 6 weeks treating 29 patients with severe chronic psoriatic plaques. The calcitriol treatment appeared to be very effective in improving erythema, induration, scaling and global severity of psoriatic plaques. The difference in clinical efficacy between calcitriol and vehicle ointment was highly significant as early as 1 week after the start of treatment. After 6 weeks, clearance of psoriatic lesions was found in 48% of calcitriol-treated sides and in 7% of vehicle-treated sides. Skin biopsies of calcitriol-treated sides revealed a reduction in epidermal hyperplasia, normalization of the keratinization process and decreased inflammation of the psoriatic skin. Calcitriol ointment did not cause cutaneous or systemic adverse reactions and did not induce disturbances of calcium and phosphorus horneo-stasis. Twice daily 3μg/g calcitriol ointment appears to be a safe and effective topical treatment for severe chronic psoriatic plaques.