Active chloride (Cl-) secretion by intestinal crypt enterocytes is the central pathophysiological disturbance in most cases of acute diarrhoea. We examined monolayers of the human intestinal cell line T84 mounted in Ussing chambers to see whether the T-cell lymphokine gamma interferon (IFN-gamma) might affect the Cl- secretory properties of these cells, which morphologically and functionally resemble native crypt enterocytes. Pretreatment of T84 cell layers with IFN-gamma for 24 h (but not for 3 h) markedly decreased the Cl- secretory response to vaso-active intestinal polypeptide (VIP) and to cholera toxin and carbachol without appreciably affecting the overall morphology, electrical resistance, or cyclic AMP response of the T84 cell monolayer. The IFN-gamma treatment, however, did induce subtle changes in the T84 cell membrane protein composition which might have affected ion channels regulating Cl- secretion. Our results may indicate a possible novel 'cell-mediated' immune mechanism through which activated gut T cells could modulate the extent of intestinal electrolyte and fluid secretion in, for example, enteric infections.