We characterized the taurine transport system in human intestinal Caco-2 cells and showed that it is subject to adaptive regulation. The activity of taurine transport in Caco-2 cells was evaluated by means of an Na+- and Cl(-)-dependent high-affinity transport system, the characteristics of which were similar to those of the beta-amino acid-specific taurine transport system previously described for various tissues. The activity of taurine transport was down-regulated on culturing in taurine-containing medium. This taurine-induced down-regulation was dependent on both the incubation time with taurine and the concentration of taurine. Hypotaurine and beta-alanine were also capable of inducing this adaptive regulation, whereas alpha-amino acids and gamma-aminoisobutyric acid were not. Kinetic analysis of control and taurine-treated cells suggested that the down-regulation was associated with a decrease in the maximal velocity of taurine transport and also with a decrease in the affinity of the taurine transporter. Cycloheximide treatment weakened the taurine-induced down-regulation. The mRNA level of the taurine transporter (HTAU type) in taurine-treated cells was markedly decreased compared with in control cells. These results indicate that a complex regulatory mechanism is involved in this down-regulation.