Background: A new class of topical receptor-selective acetylenic retinoids, the first of which is tazarotene, has been developed. Objective: Our purpose was to compare the safety, efficacy, and duration of therapeutic effect of 12 weeks of once-daily tazarotene 0.1% and 0.05% gel with that of twice-daily fluocinonide 0.05% cream in the treatment of patients with plaque psoriasis. Methods: Three hundred forty-eight patients with plaque psoriasis were enrolled and 275 patients completed a multicenter, investigator-masked, randomized, parallel-group clinical trial. Results: Both tazarotene gels were as effective as fluocinonide in reducing plaque elevation after 1 week of treatment, and tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of trunk/limb lesions at all study weeks except week 4. Tazarotene 0.1% gel was similar to fluocinonide in reducing scaling of knee/elbow lesions at weeks 8 and 12. Fluocinonide had a significantly greater effect on erythema than tazarotene at weeks 2 through 8. However, treatments were not significantly different at week 12, and tazarotene demonstrated significantly better maintenance of therapeutic effect after cessation of therapy. Conclusion: Tazarotene 0.1% and 0.05% gels were safe and effective in the treatment of mild-to-moderate plaque psoriasis.(J Am Acad Dermatol 1998;38:705-11.)