Alterations in proliferation status and cellular composition of immune organs are among key events in the modulation of immune function after burn injury. Nuclear factor (NF)-kappaB is a transcription factor that plays a pivotal role in the response to injury as well as immune cell differentiation and proliferation. In this study, we investigated the effects of burn injury on the activity of NF-kappaB and its association with cellular proliferation in the spleen. Western analysis of whole spleen tissues of mice after 18% burn injury revealed a marked reduction in nuclear NF-kappaB rel A protein expression 3 to 21 days after injury when there was an increase in proliferative activity in the red pulp of the spleen after injury as indicated by an increase in proliferating cell nuclear antigen (PCNA). In the splenic B cells, however, the down-regulation of NF-kappaB rel A was associated with decreased PCNA expression as well as IkappaBalpha and phosphorylated IkappaBalpha. In contrast, no significant change in NF-kappaB rel A or PCNA expression was observed for splenic T cells. These data suggest that there is a differential regulation of NF-kappaB and proliferative activity in the splenic cell subsets after burn injury. Furthermore, the regulation of NF-kappaB may be linked to the proliferative changes seen in the spleen after burn injury.