In WEHI-231 cells, anti-immunoglobulin (anti-Ig) treatment leads to both a decrease in the DNA-binding activity of p50/c-Rel/p53 protein complexes and a transient enhancement in the DNA-binding activity of p50 homodimeric complexes. These cells subsequently undergo apoptosis. Because IkappaB-alpha plays a pivotal role in the regulation of Rel/NF-kappaB activity, we have characterized both the nature and kinetics of the expression of IkappaB-alpha following anti-Ig-induced apoptosis in WEHI-231 cells. Anti-Ig treatment of WEHI-231 cells decreased the steady-state level of IkappaB-alpha mRNA, but enhanced the stability of IkappaB-alpha, leading to an accumulation of IkappaB-alpha in both the cytosol and nucleus. Concomitant with the increase in IkappaB-alpha expression there was a gradual decline in the nuclear expression of c-Rel. Because c-Rel plays an important role in the survival of WEHI-231 cells, these results suggest that post-transcriptional regulation of IkappaB-alpha expression might play a role in the anti-Ig-induced apoptosis in WEHI-231 cells.