To ascertain the cellular immune function of patients successfully treated for lymphoma, we measured skin-test reactivity to a battery of recall antigens, phytohemmagglutinin (PHA), and the neoantigens keyhole limpet hemocyanin (KLH) and dinitrochlorobenzene (DNCB). Seventy-four patients with Hodgkin's disease and 31 patients with non-Hodgkin's lymphoma were studied from 3 to 186 months after cessation of therapy for lymphoma. Although reactivity to recall antigens and PHA was normal, the number of patients responding to the neoantigens was significantly (P < 0.01) lower than normal (KLH, 35%; and DNCB, 34%). This impairment in reactivity to neoantigens could not be correlated with specific diagnosis, stage of disease, or type of treatment. Reactivity to DNCB was significantly (P < 0.01) improved in those patients studied more than 3 years after treatment, but the number who reacted was still markedly abnormal (17 of 33). Thus, successfully treated patients with lymphoma seem to have difficulty in responding to new foreign antigens.