We report on 14 patients who developed Hodgkin's disease (HD), were successfully treated, and subsequently developed non-Hodgkin's lymphoma (NHL). The median interval between the diagnosis of HD and the diagnosis of NHL was 136 months (range 11-336). The clinical features of the patients with HD were similar to other patients with HD. Results of biopsies showed 12 nodular sclerosis and one mixed cellularity; one was not further classified. Immunophenotypic studies in nine cases showed that the Reed-Sternberg (RS) and Hodgkin's (H) cells were LeuM1+ LCA-. The patients were treated for HD in a nonuniform manner: two received radiation therapy, four received chemotherapy, and eight received both modalities. The NHLs were usually extranodal (79%) with frequent presentation as an abdominal mass. According to the Working Formulation, six lymphomas were small noncleaved cell (four non-Burkitt's, two Burkitt's), three were diffuse large cell, and two were follicular and diffuse large cell. Three neoplasms were not classified: two lymphomas with plasmacytoid differentiation were placed in the intermediate and low-grade categories, respectively, and one neoplasm was a plasmacytoma. All 14 neoplasms had an immunophenotype typical of NHL of B-cell lineage and were LeuM1-. Seven of the 12 patients treated with combination chemotherapy experienced a complete remission of their NHL. We conclude that the clinical, histologic, and immunophenotypic findings of the NHLs in these patients are analogous to those of NHLs that occur in immunosuppressed patients, suggesting that immunodeficiency plays a role in the pathogenesis of NHLs arising after HD.