To characterize the nature of K+ and Cl- transport pathways across basolateral membrane of rabbit proximal convoluted tubule, we used quantitative video microscopy to measure cell volume changes induced by rapid basolateral K+ and Cl- concentration changes. Elevating basolateral K+ resulted in cell swelling, which was largely inhibited by replacement of basolateral Cl- with cyclamate (85%) or by addition of 2 mM Ba2+ (72%). Substitution of basolateral Cl- by NO3- enhanced cell swelling, whereas substitution of Cl- by I- did not affect the K(+)-induced volume changes. Removal of Cl- from the bath reversed the cell swelling induced by raising K+ in the bath. Steady-state cell volume was 28% greater in hypotonic medium (250 mosmol/kgH2O) than in hypertonic medium (350 mosmol/kgH2O), and the rate of increase in cell volume induced by raising K+ was three times higher in hypotonic than in hypertonic medium. Substitution of Cl- by NO3- did not alter the effect of medium osmolality on K(+)-induced cell swelling, whereas addition of 0.2 mM diphenylamine-2-carboxylate inhibited the response (63%). We conclude that K(+)-induced cell swelling results from entry of K+ and Cl- into the cell across the basolateral membrane; it is proposed that transport of KCl across the basolateral cell membrane proceeds largely through two separate conductive pathways for K+ and Cl-. Cell swelling activates KCl transport occurring via K+ and Cl- channels across the basolateral membrane.