Spontaneous regression of low-grade non-Hodgkin's lymphoma often has been reported. Proposed mechanisms of this event have included concomitant infections and enhanced cellular and humoral antitumor responses by the host. Spontaneous regression of high-grade non-Hodgkin's lymphoma is rare and has never been reported in a patient with acquired immune deficiency syndrome (AIDS). The authors report a patient with spontaneous regression of AIDS-related non-Hodgkin's lymphoma and discuss the role of host immunity in mediating spontaneous regression.