The spontaneous regression (SR) of tumor has been noted in a variety of neoplastic conditions. In non-Hodgkin's lymphoma, this phenomenon has been reported in indolent histologic subtypes, with a frequency of 10-20% in selected series. Investigators evaluating new therapies for lymphomas with a favorable histology need to be cognizant of SR's impact. Mechanisms which have been proposed to explain SR have included the role of contemporaneous bacterial or viral infection, as well as an augmented host immune response which is able to mediate tumor regression via humoral and cellular effector mechanisms. The ability to recapture immunoregulatory control is aptly illustrated by lymphomas developing after organ transplantation where reduction of immunosuppression has, on occasion, resulted in tumor regression. The importance of immune regulation of B-cell lymphoma is also suggested by the tumor's responses to immunotherapy and interferons in vivo and by the biologic and pathologic characteristic of indolent lymphomas being analogous, in may respects, to benign neoplasms. Indolent lymphomas which differ from aggressive lymphomas in their clinical and biological behavior may be more responsive to these host immunoregulatory influences. Review of clinical experience as well as proposed mechanisms of spontaneous regression in non-Hodgkin's lymphoma will be explored in this report.