Studies indicate that lymphoid tissue (e.g., thymus, bone marrow & Peyer's patches) show evidence of increase apoptosis (Ao) during sepsis. However, it is not known if mucosal lymphoid tissue, such as intestinal lamina propria (LP), also show evidence of increased Ao and if so, is this associated with functional changes in cytokine gene expression in the LP. To examine this, male C3H/HeN mice were subjected to cecal ligation and puncture (CLP) and lamina propria mononuclear cells (LPMC) were harvested at 4 (early) or 24 h (late sepsis). Alterations in the cell phenotype and Ao (Tunel assay) were determined by 3-color flow cytometry. Cytokine gene expression was assessed by RNase protection assay. Sham LPMC preparation were found to be 34.4±2.4% B220+, while 12.4±2.1% were CD8-, 22.0±0.8% were CD4+ and 6.4±0.7% were F4/80+(macrophages). The frequency of B220+ (9%*↑) and CD8+ (6%*↑) populations increased markedly at 4 h after CLP. The percent of Ao+ in CD8+, B220+ and F4/80+ cells increased markedly at both 4 and 24 h. CD4+ cells showed a marked increase in Ao only at 24 h after CLP. When cytokine mRNA expression was examined, a significant increase in IL-2, -10, and -15 gene expression was observed at 24 h after CLP. Thus, the early phenotypic changes associated with increased Ao may be a reflection of localized immune cell activation in early sepsis contributing to the increased cytokine gene expression seen in late sepsis. This localized activation may contribute to gastrointestinal inflammation and/or immune dysfunction in sepsis.