Differentiated Caco-2 cells have two kinetically distinct sodium-glucose cotransporters. Short-term incubation of Caco-2 cells with EGF resulted in an up-regulation of sodium-glucose cotransport and subsequent increase in Na+/K(+)-ATPase activity. The effect of basolaterally applied EGF was more significant with or without incubation with cholera toxin. The early effect of EGF on glucose and sodium cotransport may have important therapeutic implications in diarrhea and dehydration states. The in vitro model described here uses a homogeneous cell population and provides a versatile system for uptake and transport studies.