Differentiated PC12 cells, which become dependent on the presence of growth factors in the media and die by apoptosis after several hours of serum deprivation, were used to test the ability of IGF-1 to regulate the endogenous levels of the death-suppressing protein Bcl-xL, IGF-1 was capable of preventing apoptosis of serum-deprived differentiated PC12 cells at physiological concentrations, with optimal results seen at 10(-8) M. Incubation with the hormone resulted in a significant increase of Bcl-x mRNA after 3-6 h incubation and a doubling of Bcl-xL protein levels by 24 h incubation. Our results show that the protective effect of IGF-1 in PC12 cells is associated with an up-regulation of Bcl-xL mRNA and protein levels.