Alefacept selectively reduces memory T cells and inhibits T-cell activation. Large randomized trials have shown that intramuscular (IM) delivery of alefacept is safe and effective in treating plaque psoriasis. Subcutaneous (SC) administration of alefacept may provide advantages for some patients including convenience, ease of use, and reduced pain on injection. We conducted a randomized, open-label, crossover study in 50 healthy volunteers to determine if alefacept 15 mg administered SC is bioequivalent to alefacept 15 mg administered IM. The pharmacokinetic parameters used to determine bioequivalence were area under the serum concentration-time curve to the last measurable value (AUClast; primary endpoint), peak serum concentration (Cmax), and AUC to infinity (AUCinfinity). For each of these parameters, the 90 percent confidence intervals for the least squares mean ratios of alefacept SC to alefacept IM were well within the conventional bioequivalence range of 80 percent to 125 percent. These data, together with the finding that the mean serum concentration-time curves for alefacept were nearly identical following both routes of administration, demonstrate the bioequivalence of alefacept SC and alefacept IM. No clinically important differences between the pharmacodynamic profiles (total lymphocyte and lymphocyte subset counts) of the two routes of administration were observed. Alefacept SC and alefacept IM were similarly well tolerated. Our results suggest that SC dosing may represent a viable delivery option for alefacept.