The pleiotropic cytokine TGF-beta1 is a member of a large family of related factors involved in controlling cell proliferation, differentiation and apoptosis. TGF-beta ligands interact with a complex of type I and type II transmembrane serine/threonine kinases and they transmit their signals to the nucleus via a family of Smad proteins. A panel of over 20 Burkitt's lymphoma (BL) cell lines has been compiled including those that are Epstein-Barr virus (EBV) negative, those that carry EBV with a restricted pattern of EBV latent gene expression (group I) and those that express the full range of latent EBV genes (group III), together with selected EBV-transformed lymphoblastoid cell lines (LCLs). Most of the EBV-negative and group I BL cell lines underwent apoptosis or a G(1) arrest in response to TGF-beta1 treatment. In contrast, group III cell lines and LCLs were completely refractory to these effects of TGF-beta1. All of the cell lines expressed the TGF-beta pathway Smads and the TGF-beta type I receptor. Lack of responsiveness to TGF-beta1 appears to correlate with a down-regulation of TGF-beta type II receptor expression. Studies of EBV-converted and stably transfected BL cell lines demonstrated that the EBV gene LMP-1 is neither necessary nor sufficient to block the TGF-beta1 response.