We have studied the clinical effects of a murine monoclonal anti-human T-cell antibody in seven patients with T-cell lymphoma. Four to 17 treatments with anti-Leu-1 were given to each patient over periods of 14–75 days. Doses of antibody ranged from 250 micrograms to 100 mg. Antibody treatments usually caused a rapid fall in circulating T cells, with return to baseline levels within 24–48 hr. The optimum dose appeared to vary for each patient. Clearance of circulating tumor cells correlated with the amount of antibody bound to cells. Other than dyspnea in one patient, no serious toxicity was noted. Five patients had definite tumor responses, but these were of short duration (1.5–4 mo). Four patients developed anti-mouse immunoglobulin (Ig) antibodies, and in three patients, this was responsible for tumor escape from therapy. Although 95% of the host anti-mouse Ig response was directed against mouse Ig constant region determinants, a small but significant component was found to be antiidiotype.