The tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) is a member of the recently defined TRAF family. It takes part in the signal transduction of the TNF receptor 2 (TNFR2), the lymphotoxin-beta receptor (LT-betaR), CD40, CD30, and LMP1; is induced by LMP1 in vitro; and protects lymphoid cells from apoptosis. To identify the cells in which TRAF1 is active in vivo, we studied TRAF1 transcripts in normal lymphoid tissue, in Epstein-Barr virus (EBV)-induced lymphoproliferations, and in malignant lymphomas with special reference to those that overexpress the cytokine receptor CD30 and CD40 of the TNF receptor family at the single-cell level using a radioactive in situ hybridization. In normal lymphoid tissue, TRAF1 message proved to be absent from all resting B and T cells as well as from macrophages and accessory cells (follicular dendritic cells and interdigitating cells) and present in few perifollicular and intrafollicular lymphoid blasts. In contrast, there was a high and consistent TRAF1 overexpression in EBV-induced lymphoproliferations and Hodgkin's disease. Nearly all non-Hodgkin's lymphoma show low or no TRAF1 expression. Only some cases of diffuse large B-cell lymphoma showed a moderate to high TRAF1 signal. Several of the latter cases were EBV+. These data confirm that TRAF1 is an inducible molecule and indicates its deregulation in the mentioned disorders with the potential of a blockage of the apoptotic pathway.