Examination of risk factors that may be responsible for the increasing incidence of non-Hodgkin's lymphoma (NHL) over the past few decades would be incomplete without considering familial aggregation of hematolymphoproliferative neoplasms and the relative contributions of heredity and environment to the etiology of NHL. Reports of families with two or more NHL cases and sometimes additional members affected by other hematopoietic malignancies (multiple-case families) are summarized, as are findings from surveys and quantitative risk estimates from population-based studies of familial aggregation. The notable occurrence of various immunological abnormalities among multiple-case family members with and without NHL or related neoplasms is underscored, as is the diversity of types of other lymphoproliferative and hematopoietic malignancies among close relatives in these families. Preliminary evidence suggesting that multiple-case families may be more susceptible to certain environmental exposures is presented. An international registry of such families (particularly those identified in population-based studies) is proposed to clarify the interrelationship of genetic, familial, and environmental factors in the etiology of NHL.