Intestinal epithelial cells (IEC) are known to secrete a number of important cytokines. Recently, we determined that IEC-derived IL-6 and TGF-beta could enhance IgA secretion and suppress IgM secretion by isolated mucosal B cells. However, since the IEC-derived cytokines must function in the context of locally produced T cell cytokines, the effect of IEC- and T cell-derived cytokines on mucosal B cell immunoglobulin secretion was determined. Using 4 day culture supernatants (IEC-SN) from the rat IEC-6 intestinal epithelial cell line and lipopolysaccharide (LPS) stimulated Peyer's patch or mesenteric lymph node B cells, the IEC- SN was found to act with IL-2 to greatly enhance IgA secretion but limit or suppress IgM secretion as compared to cultures of LPS stimulated B cells alone. However, neither IL-4, IL- 5, nor IFN-gamma affected IgA secretion with the IEC-SN. Depletion of the IEC-SN with specific anti-cytokine antibodies suggested that IEC-derived TGF-beta and IL-6 were both responsible for the enhancing effect along with IL-2 on IgA secretion, whereas IEC-derived TGF-beta alone limited or suppressed IgM secretion. These results suggest that cytokines derived from local IEC and T cells may create an environment which may contribute to the preferential enhancement of IgA secretion seen in mucosal tissues.