The mechanism of quinapril's interaction with the organic anion transporter was characterized by studying its effect on the transport of p-aminohippurate (PAH) in rabbit renal basolateral membrane vesicles (BLMV). Cis-inhibition studies demonstrated that quinapril was a specific and potent inhibitor of PAH. The Ki of quinapril was about 20 microM, a value similar to that of probenecid and eight-times lower than the K(m) value of 165 microM for PAH. Even though quinapril resulted in trans-inhibition of PAH uptake during counterflow studies, kinetic studies revealed that quinapril was a competitive inhibitor of PAH transport. This latter findings suggests that quinapril and PAH share a common binding site on the transporter. Overall, the results indicate that quinapril is a high-affinity inhibitor of the organic anion transporter in renal BLMV, and that drug-drug interactions may occur with other organic anions at the basolateral membrane of proximal cells.