The angiotensin-converting enzyme (ACE)-inhibitor ceronapril (SQ 29852) is shown to be a substrate of the intestinal dipeptide transporter. Uptake by Caco-2 cells, grown as confluent monolayers, follows a major saturable pathway ( K m, 0.91 ± 0.11 mM; ∼90% at 1 mM) together with a minor passive component ( k J, 32.3 ± 6.6 ng (10 6 cells) −1 (20 min) −1. Uptake was inhibited by competition with dipeptides such as l-AIa- l-Pro (K i, 2.96 mM) and l-Phe-Gly ( K i, 3.84 mM) but not by cephalosporins such as cephalexin. In contrast, transport was non-saturable, flux increased linearly with concentration and data were consistent with a passive transepithelial transport mechanism. Transport profiles showed a biphasic dependence upon time with an initial flux of 0.83 ± 0.02 ng insert −1 min −1 ( k 1) and a terminal value of 1.65 ± 0.08 ng insert −1 min −1 ( (k 2 ) at 100 μM. It is concluded that the basolateral efflux is retarded so that the passive paracellular transport controls the overall transepithelial transport characteristics in the Caco-2 model. Carrier-mediated uptake into intestinal enterocytres, followed by rate-limiting basolateral efflux, may explain the extended t max in vivo following oral administration.