Human B-cell lines established from Burkitt lymphoma (BL) and normal B cells immortalized in vitro by EBV (LCLs) differ in phenotype. While the BL correspond to resting B cells, the LCLs resemble activated B cells. When BLs which have the EBV genome are carried in vitro, they acquire some of the features of LCLs, such as expression of B-cell activation markers and the tendency to form aggregates. Comparison of several B-cell lines for sensitivity to TGF-beta showed that the growth of BLs (with few exceptions), but not of the LCLs, was inhibited. The results suggested that the sensitivity to TGF-beta correlates with the cellular phenotype. In the present work, this assumption is even more critically substantiated by studying 2 sublines of an EBV-genome carrying BL line, Mutu, which were selected for single cells and aggregates. The former (with resting phenotype) was inhibited, while the subline of aggregated cells, which also expressed B-cell activation markers, was not inhibited. Somatic-cell hybrids between BLs, LCLs and non-B cells provided lines with phenotypic differences. Results with a panel of such hybrid lines also showed that those which express the activated B-cell phenotype are not inhibited by TGF-beta. Differences in the levels of expression of activation markers did not influence the response to TGF-beta.