Recent work on kidneys from hypophysectomized (hypox) rats has shown atrophy of the proximal tubules with no effects on the other parts of the nephron. We carried out experiments to determine whether the reduction of p-aminohippurate (PAH) is consistent with structural changes in the proximal tubule of hypophysectomized rats. Initial velocities of PAH uptake by renal cortical slices were found to be constant over 30 min of incubation at concentrations of PAH up to 0-5 mmol/1 for both control and hypox animals. Using kinetic analysis, it was found that both maximal velocity, Vmax, and the Michaelis constant, Km, were reduced in hypox animals, the relative reduction being similar for both parameters. Comparison between high Na (100 mmol/1) and low Na (6 mmol/1) media indicated that in both control and hypox rats, Vmax was significantly lower in low Na medium than in high Na medium, whereas Km was not changed. Efflux of PAH from pre-loaded tissue also showed a reduction in hypox animals. These results may indicate that hypophysectomy alters the capacity of PAH transport in renal cortical slices by (1) reducing the effective transport area or sites, and (2) by changing carrier-substrate affinity.