Background: The excimer laser delivers targeted ultraviolet B 308-nm radiation. Objective: This investigation evaluated the efficacy of multiple, medium-dose excimer 308-nm laser treatments for psoriasis. Methods: Twenty volunteers with plaque psoriasis were enrolled. Six plaques received treatment 3 times per week for up to 8 weeks; another plaque served as a control. As in standard phototherapy, a flexible dose escalation scheme was implemented during the course of treatment. Modified Psoriasis Area and Severity Index scores were rendered throughout the study with follow-ups at 1, 2, 4, and 6 months. Results: Fifteen subjects completed the study without complications. The mean number of treatments to achieve >95% clearance was 10.6. The mean cumulative UV radiation dose was 6.1 J/cm², and the mean remission time was 3.5 months. Conclusion: A thrice-weekly, medium-dose irradiation schedule with the 308-nm laser can effectively clear localized plaque-type psoriasis in fewer treatments with an overall lower cumulative dose, compared with standard phototherapy. This innovative UV device allows specific targeting of affected sites without needless exposure of unaffected skin. (J Am Acad Dermatol 2002;47:701-8.)