Background: Various treatments including corticosteroids, nonsteroidal anti-inflammatory drugs, D-penicillamine, interferon gamma, cyclosporine, and cytostatic drugs have been used with limited success in both morphea and systemic sclerosis (SSc). Objective: We investigated the effect of treatment with oral calcitriol in patients with localized or systemic scleroderma. Methods: A randomized, double-blind, placebo-controlled study of 9 months' duration with a 6-month follow-up was performed at the Department of Dermatology. A total of 27 patients (7 patients with SSc and 20 with morphea) were selected on a minimal skin score of 3 for patients with morphea and 12 for those with SSc. Each patient received calcitriol (0.75 μg/day for 6 months plus 1.25 μg/day for 3 months) or placebo for 9 months. Efficacy parameters included skin score, measurement of serum markers of collagen synthesis and degradation and, additional for the patients with SSc, oral aperture measurements, lung function studies, and esophagus motility. Results: The skin score in patients with morphea after 9 months' treatment showed no significant difference between the placebo and calcitriol groups (mean percentage reduction [SD] in skin score in the placebo group was −29.3 [57.9]; in the calcitriol group it was −19.4 [46.6]). The small group of patients with SSc was inadequate to allow us to draw any conclusions regarding efficacy. No significant change was found in the serum markers of collagen metabolism. Conclusion: In this study calcitriol was not more effective than placebo in patients with morphea. Because of the small group of patients with SSc treated, no conclusions regarding efficacy in SSc can be drawn. (J Am Acad Dermatol 2000;43:1017-23.)