c-Rel induction in activated lymphocytes is suppressed by the immunosuppressive drug, FK506. Here we show that FK506-suppressible, delayed c-Rel induction is similar in B and T cells and is regulated by mRNA production. In contrast, rapid nuclear translocation of pre-existing cytoplasmic c-Rel occurs only in B cells, but not in T cells. Analysis of I-kappaBalpha and -beta in these cells showed that both I-kappaBalpha and I-kappaBbeta were rapidly degraded in response to stimulation in B cells, but only I-kappaBalpha was affected in T cells. These observations suggest that 1) different Rel proteins in the same cell may be sequestered in the cytoplasm differently, 2) the sequestration mechanism is cell-type specific, and 3) differential sensitivities of I-kappaBalpha and beta in B and T cells may regulate, in part, the rapid response of family members. We propose that subunit-specific and cell-specific regulation of nuclear translocation may help determine the varied cellular responses to different stimuli.