1. In order to further define the action of atrial natriuretic peptide (ANP) on proximal tubular (PT) transport, combined clearance and electron microprobe X-ray (EMPX) experiments were performed on five male Wistar rats infused with ANP (0.16 nmol/kg per h) and nine control animals. 2. Electron microprobe X-ray analysis of PT cell electrolytes (mmol/kg wet weight) revealed a similar [Na]i in both the control and ANP treated groups (16.4 +/- 0.4 vs 16.5 +/- 0.4; P = 0.894). [Cl]i was lower in the ANP treated animals (14.8 +/- 0.3 vs 12.0 +/- 0.3; P < 0.0001) as was [K]i (131.4 +/- 1.4 vs 114 +/- 1.7; P < 0.0001). The PT cells in the ANP treated group had a significant reduction in dry weight (20.1 +/- 0.3 g% vs 19.0 +/- 0.3 g%; P < 0.024), indicating significant cell swelling. Thus, despite a normal [Na]i, there was net accumulation of Nai following ANP treatment. 3. These results are consistent with accumulation of Nai due to inhibition of the Na pump followed by cell swelling and subsequent regulatory volume decrease with exit of K and Cl. These results are the first to show the effect of ANP on PT intracellular electrolytes.