The process by which endogenous retroviral superantigen (vSAg29) expressing SJL lymphomas (RCS) stimulate host CD4+Vβ16+ T cells, in order to elicit help (notably IL-4 and -5) for their growth, has been characterized as “reverse immune surveillance”. This response is facilitated by the high expression of an array of co-stimulating molecules on RCS cells, including B7.1, B7.2, 41BBL, CD40 and CD30. On the basis of their germinal center derivation, SJL lymphomas bear close resemblance to a subpopulation of human germinal center B cell lymphomas, such as CD30+ Hodgkin’s lymphomas. In our earlier studies, growth of transplantable SJL lymphoma (RCS-X) in vivo was inhibited by anti-CD30 mAb. While the evidence shows that this effect is indirectly on the lymphoma-responsive CD4 T cells, the mechanism of action was unclear. To shed light on the role of CD30-CD30L interactions in SJL lymphoma development, CD30L-/- were bred onto SJL background and tested for their support of transplantable lymphoma growth. A significant reduction in lymph node (17.4-54.7%) and spleen weights (21.5-38.2%) was observed for CD30 null mice, compared to wild type SJL mice. Despite this reduction in the lymphoid compartment, no reduction in lymphoma growth was observed. The results suggest that while CD30-CD30L interactions might be important for SJL lymphoma growth, other costimulating molecules might contribute significantly to the process of reverse immune surveillance in RCS lymphoma.