Earlier studies indicate that the micro ora contains mitogens to intestinal epithelial cells. Our aim is to examine whether cell wall components of both Gram-negative and positive bacteria in uence cell proliferation in small intestinal and colonic epithelial cells. A human colonic epithelial cell line from adenocarcinoma (IEC-6) and a nontransformed small intestinal cell line from germ-free rats (LS-123) were incubated with (a) lipothecoid acid from Streptococcus faecalis at 1.56 -50 mg:ml, (b) peptidoglycan from Staphylococcus aureus at 0.1 -7.5 mg:ml, (c) lipopolysaccharides (LPS) from Escherichia coli, Klebsiella pneumonia and Pseudomona aeruginosa at 0.1 -7.5 m g:ml, (d) lipid A from Escherichia coli at 0.016 -50 m g:ml. The cells were labelled with tritiated thymidine and processed for autoradiography. DNA synthesis was estimated by the labelling index.Cell wall components of Gram-positive bacteria (LTA from Streptococcus faecalis and peptidoglycan from Staphylococcus aureus) moderately increased the DNA synthesis in both cell lines (p B0.001). Similarly, cell wall components of Gram-negative bacteria (LPS of Escherichia coli, Klebsiella pneumonia and Pseudomona aeruginosa and lipid A of Escherichia coli increased the labelling index in IEC-6 and LS-123 cells (p B0.001).Thus, this study identi es mitogens present in both Gram-positive and Gram-negative bacteria that increase cell proliferation in rat and human intestinal cells. Our ndings support a role for the micro ora in the regulation of cell proliferation in both health and disease.