The presence of activated CD4⁺T lymphocytes in psoriatic skin plaques suggests an immune-mediated pathogenesis for the disease. Six patients with recalcitrant plaque psoriasis (PASI>12) received a humanized non-depleting monoclonal antibody to CD4 (ORTHOCLONE OKT^®cdr4a). The antibody was well tolerated. Four weeks from treatment, the mean decrease in PASI score was 46%. In three patients disease remission was prolonged for up to 6 months and, in one case, up to 1 year post-treatment. In all patients, circulating CD4⁺T-cell counts remained normal and peripheral OKTcdr4a-coated CD4⁺lymphocytes were detected up to 10 days after antibody infusion. These results point to the relevance of CD4⁺lymphocytes in psoriasis. They also emphasize that depletion of CD4⁺cells is not mandatory to achieve therapeutic effectiveness.