Aging alterations in the renal transport of p-aminohippurate (PAH) were investigated using cortical slices from C57BL/6 mice and standard clearance techniques in 5-ethyl-5-(1-methylpropyl)-2-thiobarbituric acid (Inactin)-anesthetized Fischer 344 rats. Life-span stages were classified as growth, maturity, and aging. PAH uptake was linear from 0 to 20 min with steady state occurring at 30 min in the growing and mature mouse and 20 min in the aging mouse. Km values for PAH uptake in the growing, mature, and aging mouse were 250, 123, and 643 microM, respectively, and maximal rate of uptake values were 0.756, 0.926, and 0.586 mumol X g-1 X 30 min-1, respectively. The efflux half-life (t 1/2) for PAH was similar in all age groups. The PAH acetylation rate was similar in the growing and mature mouse but decreased by 40% in the aging mouse. There were statistically significant correlations between aging (12-27 mo) and renal plasma flow [(RPF) r2 = 0.33, P less than 0.05] and between aging and tubular maximal (Tm) activity for PAH transport (r2 = 0.84, P less than 0.001). Maximal decreases of 25 and 40% were found for RPF and Tm, respectively, in the aging rat. It is concluded that aging affects PAH transport at the receptor level.