I mmunologic function was evaluated in 12 patients with Hodgkin's disease and 5 patients with lymphocytic lymphoma who had been successfully treated with either chemotherapy, radiation therapy, or both of these modalities 3-42 mo previously. Only two of the patients were found to have total anergy to a battery of six recall skin test antigens and all were responsive to skin testing with phytohemagglutinin. However, 10 of 16 patients were unable to develop delayed cutaneous hypersensitivity to either of the neoantigens dinitrochlorobenzene or keyhole limpet hemocyanin. Four other patients developed reactivity to only one of these neoantigens for a total of 14 of 16 (88%) of the patients demonstrating some impairment in neoantigen response. Total lymphocyte, T-lymphocyte, B-lymphocyte, and null cell numbers, as well as serum immunoglobulins were quantitatively normal. Monocyte numbers, chemotaxis, and Fc receptor activity were normal. Monocyte staphylocidal activity at 60 min was modestly depressed and candidacidal activity was depressed in those receiving both chemotherapy and radiation therapy. Spontaneous (unstimulated) lymphocyte [3H]thymidine incorporation was low in the patients as a group and lymphoblastic transformation to specific antigens was impaired in 11 of 17 patients who had positive skin test reactions to the same antigen. Highly significant suppression of lymphoblastic transformation was noted after stimulation by the mitogens phytohemagglutinin, pokeweed, and concanavalin-A. The greatest impairment of mitogen response was seen in those patients receiving both chemotherapy and radiation therapy. These data demonstrate specific impairments of neoantigen processing, lymphocyte function, and to a lesser extent monocyte function in successfully treated patients with lymphoma. These impairments may contribute to the increased incidence of infections and second primary malignancies in these patients.