Approximately 3% of acquired immunodeficiency syndrome cases present with non-Hodgkin's lymphoma. By 6 to 8 years after human immunodeficiency virus infection, lymphoma risk is elevated 100-fold, and the risk approaches 1% per year following acquired immunodeficiency syndrome diagnosis. The proportions presenting as lymphoma differ by age, sex, and race, with relative rates being higher in older persons, males, and whites. The differences are similar in magnitude and direction to those seen in non-human immunodeficiency virus-infected persons and account for the variation by risk group. The relative risk of high-grade lymphoma is greatest, but significant increases are also seen for some intermediate-grade tumors. At diagnosis, persons with Burkitt's lymphoma, more common in children, have significantly higher average CD4 counts than those with immunoblastic tumors. Human immunodeficiency virus-associated lymphoma risk is probably related to dysregulation of the immune system leading to uncontrolled proliferation of transformed cell clones and subsequent genetic accidents. Environmental factors are unlikely to be important. By 1994, 10% of all lymphomas will be human immunodeficiency virus related, but this proportion will increase in the future. New approaches to the therapy of lymphoma are needed for this tumor, which we can neither prevent nor adequately treat.