The passage of nickel across monolayers of intestinal epithelial Caco-2 cells, originally derived from a human colonic adenocarcinoma, was studied in bicameral chambers. The results showed that the transport and accumulation of nickel were depressed in iron-loaded monolayers, indicating that the metal participates in an absorptive process for iron in the Caco-2 cells. No detectable transport of nickel in either the apical to basal or basal to apical direction occurred at 4 degrees C. Since cellular metabolism is inhibited at 4 degrees C, these data indicate that there is no passive transcellular or paracellular passage of the nickel across the monolayers. Studies in ATP-depleted monolayers showed an increased permeability of nickel, and concomitantly there was a similar increase in the permeability of the paracellular marker mannitol, These results indicate that the metabolic inhibition results in a loosening of the junctional complexes between the Caco-2 cells, resulting in a paracellular leakage of the nickel. Additional experiments showed that the transport of nickel in the basal to apical direction occurred at a higher rate than in the apical to basal direction, This indicates the presence of an extrusion mechanism that secretes the nickel from the basal to the apical side of the Caco-2 cells. Studies with Caco-2 cells and in vivo studies by other authors have shown similar results for other metals, indicating that colonic epithelial cells may have the ability to secrete some metals, (C) 1998 Academic Press.