Objectives. Alefacept is a biologic response modifier indicated for moderate to severe psoriasis; it has been available since 2003. It is typically administered in a dosing regimen of 15 mg intramuscularly (IM) weekly for 12 weeks. The purpose of this study was to determine whether a higher dose may be more beneficial in achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI 75). A secondary objective of this study was to examine whether increasing the dose during the initial course of alefacept would reduce the time to onset of efficacy and overall response rate. Two separate dosing regimens are evaluated in this study: 30 mg IM for 6 weeks followed by 15 mg IM for 6 weeks (group 1) and alefacept 30 mg IM weekly for 12 weeks (group 2). Methods. Efficacy was assessed using the PASI, Physician Global Assessment, body surface area, and photographic evaluation of a target lesion. A total of 20 patients enrolled and were randomized, 16 of whom completed the study. Data analyses were performed on a per-protocol basis. Results. Overall, the mean PASI scores progressively decreased, with 43.8% reaching a 50% reduction in the PASI (PASI 50) at week 14 evaluation. Of these participants, 37.5% were in group 1 and 50% were treated with alefacept 30 mg IM for 12 weeks (group 2). Although our sample size was small, 12.5% of patients (one patient in each treatment arm) reached PASI 75. The most common adverse events encountered in this trial were mild infection, headache, pruritus, and erythroderma. There were no infections associated with a CD4+ cell count <250 cells/mm3. Conclusions. There was no difference between the treatment groups in achieving PASI 50 or PASI 75. In addition, in our small population, the higher doses of alefacept were associated with increased adverse effects, including erythroderma. © 2008 by Le Jacq.