Transforming growth factor beta 1 (TGF beta 1) is an antiproliferative and proapoptotic cytokine for normal B-cells, however many B-cell lymphomas have lost their response to TGF beta 1. The aim of this study was to identify the sequence of events in apoptosis induced by TGF beta 1 in an EBV negative, human B-cell lymphoma line (HT58). The proportion of apoptotic cells increased gradually (up to 72 hr) at an optimal dose range of 0.5-1.0 ng/ml. The induced cell death required the action of downstream caspases. Caspase activation was accompanied by an increase in the permeability of mitochondrial membranes, but there was no change in the expression of certain members of Bcl-2 family (Bcl-2, Bax, Bcl-XL). Similarly, none of the death receptors or ligands were involved in apoptosis induction. Further study will include the participation of TGF beta 1 target genes in the pore formation of mitochondrial membranes and/or the elimination of a putative survival signal.