We have investigated the biological and therapeutic properties of a humanized anti-CD4 MoAb, hIgG1-CD4, in patients with refractory psoriasis and rheumatoid arthritis (RA). hIgG1-CD4 is a modulating, non-depleting MoAb, which induced a first-dose reaction in most patients treated. It provided brief symptomatic relief in both conditions, and psoriasis appeared easier to control with conventional agents after MoAb therapy. At the doses used, hIgG1-CD4 did not synergize therapeutically with the panlymphocyte MoAb CAMPATH-1H (C1H) in patients with RA treated sequentially with both agents. There were no serious adverse effects definitely attributable to therapy. Our results are compared with those of other CD4 MoAb studies, and factors influencing the outcome of therapy are discussed.