Total parenteral nutrition (TPN) may cause increased rates of bacterial translocation (BT), possibly due to a loss of epithelial integrity, Cultured epithelial cells have been shown to lose tight junction integrity with interferon gamma (INF-gamma) an action which may be blocked by transforming growth factor beta (TGF-beta), Because intraepithelial lymphocytes (IEL) are a rich source of these cytokines in the epithelium, we hypothesized that changes in the IEL, while mice were receiving TPN, may be responsible for the mediation of such cytokine responses. C57BL/6 mice were randomized to a Control group which received intravenous saline and mouse chow, or a TPN group which received intravenous TPN with no oral feeding. At 7 days mice were assessed for BT, Isolated IEL were stained for CD4, CD8, and CD44 (as a marker for memory T-cells) and how cytometry was performed. mRNA was extracted from remaining IEL for cytokine expression. Reverse transcriptase polymerase chain reaction was performed to detect TGF-beta 1 and INF-gamma mRNA expression, Densities were standardized to beta-actin expression. The incidence of BT to mesenteric lymph nodes was 40 and 12.5%, for the TPN and Control groups, respectively. TPN led to statistically significant decreases in the CD4+, CD8-; CD4+, CD8+; and the CD8+, CD44+ IEL subpopulations (P < 0.05). mRNA expression for INF-gamma was increased by 53% (P < 0.05), and TGF-beta 1 mRNA expression was decreased by 75% (P = 0.1) in the IEL of TPN mice when compared with Controls. TPN led to significant changes in the IEL. Such alterations of the IEL phenotype and function may be a critical mechanism by which epithelial integrity is lost. (C) 1998 Academic Press.