We assessed the role of size, solubility, and prophagocytic cytokines interferon-gamma (IFN-gamma), and granulocyte-macrophage colony stimulatory factor (GM-CSF) in antigen uptake and kinetics by intestinal epithelial cells using keyhole limpet hemocyanin and ovalbumin. Both fluoresceinated keyhole limpet hemocyanin (3000-7500 kDa) and fluoresceinated ovalbumin (45 kDa) were internalized by human colonic epithelial cell lines, with kinetics similar to those of fluoresceinated tetanus toxoid, and there was decreased uptake of insoluble immune complexes and no enhancement in the uptake of soluble immune complexes. In addition, neither IFN-gamma nor GM-CSF altered the kinetics of uptake nor enhanced antigen internalization by the intestinal epithelial cell lines. These data suggest that regardless of the size of the soluble antigen, the presence of prophagocytic cytokines, or the formation of soluble immune complexes, fluid phase endocytosis of antigen by intestinal epithelial cells appears to be a relatively stable process.