In an 8-week double-blind trial of sulfasalazine for the treatment of moderate-to-severe psoriasis, 23 and 27 patients received the active and placebo tablets, respectively. At the end of the double-blind phase, there were 17 assessable patients receiving sulfasalazine; 7 (41%) had marked improvement, 7 (41%) had moderate improvement, and 3 (18%) demonstrated minimal change. Only 1 patient receiving placebo demonstrated moderate improvement, whereas the rest had minimal improvement or worsening of psoriasis. When the randomization code was broken, patients receiving sulfasalazine were allowed to continue therapy for an additional 4 weeks in an open manner, while those using placebo left the study. Six of 23 patients discontinued sulfasalazine therapy during the double-blind phase because of side effects, 4 due to the development of a cutaneous eruption and 2 due to nausea. Fourteen of 17 patients, who were assessable at the end of the 8-week double-blind phase, completed the additional 4 weeks of sulfasalazine therapy. Of these 14 patients, marked improvement occurred in 8 (57%), moderate improvement in 2 (14%), and minimal improvement in 4 (29%), compared with pretherapy. The low incidence of severe side effects makes sulfasalazine a consideration for oral therapy in patients whose disease severity does not justify use of methotrexate, etretinate, or psoralen plus UV-A, but whose disease severity is too widespread for safe and practical use of topical corticosteroids.