Transport of paraquat (PQ), a cationic herbicide, was investigated in a proximal renal epithelial cell line, LLC-PK1. Collagencoated permeable filters were used to study the direction of PQ transport. PQ was transported predominantly from the basolateral to apical (B-->A) membrane of these cells. The B-->A flux and uptake of PQ were saturable with time and increasing concentrations, energy dependent and inhibited by several cations. Quinine was the most potent inhibitor of basolateral PQ uptake, followed by cimetidine and then tetraethylammonium acetate (P < .0001). The noninhibitable basolateral uptake of PQ has an apparent K(m) of 357 microM and a Vmax of 1.47 pmol/micrograms protein/2 min. For flux studies, only quinine inhibited the B-->A flux of PQ (P = .02). Putrescine, p-aminohippurate, probenecid, N-methylnicotinamide and choline did not inhibit the flux or uptake of PQ. 5-N,N-Hexamethylene amiloride, a cationic amiloride analog and a potent inhibitor of the Na/H exchanger, significantly inhibited the uptake of PQ from either side (P < .0001). Acidic pH in the apical medium inhibited the uptake of PQ from either side. The studies demonstrated that PQ was actively transported by the LLC-PK1 cells. PQ shared a similar transport system with several cations, which appeared to have a more significant inhibition on the transcellular uptake than the flux of PQ.