Intracellular microelectrodes were used to investigate rheogenic Na+ (HCO3-)n cotransport in different segments of isolated proximal straight tubule (PST) of rabbit kidney. In the first portion (S2 segment) the peritubular cell membrane potential Vb averaged -46.0, SE +/- 1.3 mV (n = 20), while in terminal portion (S3 segment) it averaged -68.3, SE +/- 2.5 mV (n = 10). This difference may reflect different modes of anion permeation across the peritubular cell membrane. In S2 segments, sudden 10:1 reduction of bath HCO3- concentration caused a fast transient cell depolarization, delta Vb = -45.8, SE +/- 1.2 mV (n = 33) as expected from the presence of Na+ (HCO3-)n cotransport. As the puncture site moved further distally, delta Vb declined and gradually changed its time course by superposition of a slower secondary depolarization. In this region the transient cell depolarization could be recuperated by inhibiting the peritubular K+ conductance with Ba2+ (1 mmol/l). In S3 segments, however, the HCO3(-)-dependent transient cell depolarization was completely lost both in the absence and presence of Ba2+. In addition, sudden reduction of bath Na+ concentration did not acidify the cell, as it did in the S2 segment. The data indicate that the expression of Na+ (HCO3-)n cotransport in the peritubular cell membrane gradually diminishes towards the end of the S2 segment and is lost in the S3 segment.