The effect of cytokines on the taurine uptake by human intestinal epithelial Caco-2 cells was investigated. Among the various cytokines tested, tumor necrosis factor alpha (TNF-alpha) markedly increased the taurine uptake by Caco-2 cells, resulting in an increase in the intracellular taurine level. TNF-alpha did not induce up-regulation of the taurine uptake in hepatic HepG2, renal human embryo kidney 293, and macrophage-like THP-1 cells. The uptake of glycine, L-leucine, and L-glutamic acid by Caco-2 cells was not affected by TNF-alpha. A kinetic analysis of the taurine uptake by TNF-alpha-treated Caco-2 cells suggests that this up-regulation was associated with both an increase in the amount of the taurine transporter (TAUT) and an increase in its affinity. TNF-alpha-treated cells showed a higher mRNA level of the TAUT than did the control cells.