Compelling evidence implicates peripheral immune activation in the pathophysiology of preeclampsia. Polymorphonuclear neutrophils appear to be the cells most strongly affected, with changes in expression of surface markers and release of granule enzymes. Here, we investigated activation in additional leukocyte populations among women with preeclampsia. We used flow cytometry to evaluate changes in leukocyte markers in preeclampsia compared with uncomplicated pregnancy. To gain insights into intracellular pathways involved in leukocyte activation, we monitored the NF-kappaB signal transduction pathway. Plasma levels of interleukin-6 (IL-6) were also studied as an additional indication of cellular activation. Preeclampsia is associated with changes in L-selectin (CD62L) on neutrophils (P = 0.004), monocytes (P = 0.013), and T cells (P = 0.048) when compared with normal pregnancy. These changes include an increase in nuclear translocation of NF-kappaB and increased levels of IL-6 (P = 0.005). These findings are consistent with the presence of a generalized phenomenon of immune activation in preeclampsia.