Tacalcitol, 1-alpha,24(R)-dihydroxy vitamin D3, is an analogue of calcitriol, 1-alpha,25-dihydroxy vitamin D3. Topical tacalcitol used twice daily has been shown to be effective in the treatment of stable plaque psoriasis. The optimal concentration for once-daily treatment is, however, unknown. A randomized, double-blind comparison of seven concentrations of tacalcitol (0.25–16μg/g), tacalcitol vehicle ointment, hydrocortisone butyrate 0.1%, betamethasone dipropionate 0.05%, calcipotriol (50μg/g) and an untreated control area was therefore performed in 50 patients. The ointments (16 mg) were applied once daily to 11 2-cm circular areas of lesional psoriatic skin for 23 consecutive days. On days 1, 6, 11, 16, 20 and 24 the test areas were scored according to improvement. Erythema, infiltration and scaling were judged on a four-point scale and healing was judged in percent. The test system was sensitive and able to differentiate between the three positive controls: hydrocortisone butyrate, calcipotriol and betamethasone dipropionate. Tacalcitol at and above 1μg/g produced a time-dependent effect on psoriasis which was significantly better than the vehicle control (P0.05). The efficacy was concentration dependent up to a maximum of 4μg/g. Using 4μg/g the mean scores decreased from day 1 to day 24 as follows (95% confidence limits in parentheses): erythema, 2.64 (2.50–2.78) to 1.94 (1.76–2.12); infiltration, 2.48 (2.32–2.64) to 1.20 (1.01–1.39); scaling, 2.29 (2.11–2.47) to 1.26 (1.09–1.43); total score, 7.41 (7.00–7.80) to 4.4 (3.9–4.9). The mean degree of healing on day 24 was 50% (42–57%). In contrast, the vehicle control demonstrated only minor improvement on day 24 with a total score of 6.0 (5.5–6.5) and an average healing of 20% (13–27%). Topical tacalcitol treatment once daily demonstrated efficacy in psoriasis with a maximal effect at 4μg/g.