Interleukin-6 (IL-6) is a well-known survival/growth factor for murine B- cell hybridoma 7TD1 cells. In this study, we analyzed the behavior of 7TD1 cells in the absence or presence of IL-6. After IL-6 deprivation, the cells became growth arrested and demonstrated signs considered to be hallmarks of apoptosis. To assess the underlying molecular mechanism of IL-6-regulated apoptosis, two chemical compounds, cycloheximide (CHX) and aurintricarboxylic acid (ATA), were used to treat the cells. ATA, a DNA endonuclease inhibitor, efficiently prevented DNA fragmentation and increased cell survival in the absence of IL-6. CHX, an inhibitor of protein synthesis, failed to prevent apoptosis and blocked cell survival signals induced by IL-6. These results suggest, first, that IL-6 promotes 7TD1 cell survival by inhibiting an endogenous constitutive cell death program and, second, that this inhibition requires de novo protein synthesis. © 1994 Academic Press, Inc.