Psoriasis is a skin disorder characterized by hyperproliferation of epidermal keratinocytes. 1α,25-Dihydroxyvitamin D3 (1α,25(OH)2D3) and its analogs have been shown to inhibit keratinocyte proliferation in vitro and to be therapeutically effective for the treatment of psoriasis. Some patients with psoriasis, however, do not have a favorable response to 1α,25(OH)2D3 therapy. To evaluate the differential responsiveness to 1α,25(OH)2D3 treatment, we examined the expression of vitamin D receptor mRNA in psoriatic lesions by reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate de-hydrogenase as an internal control. In this double- blind clinical trial, we recruited 18 patients who received topical treatment of la,25(OH)2D3 (15 μg/g Vaseline) or placebo on separate psoriatic lesions for 8 weeks. In patients who showed >90% clinical im- provement of their psoriatic lesions treated with 1α,25(OH)2D3 (n = 9), an increase of 130 ± 37% in vitamin D receptor mRNA level was observed in 1α,25(OH)2D3-treated lesions when compared with the corresponding placebo controls. There was no increase in vitamin D receptor mRNA level in the lesions treated with this drug in patients who did not respond to the treatment. These data suggest that the antiproliferative activity of 1α,25(OH)2D3 is closely associated with the expression of its cognate receptor.