The developmental aspects of the renal uptake of 3-OH-3-CH3-glutaric acid (HMG) was examined using isolated renal tubules prepared from both newborn and adult rats and isolated renal brush border membranes vesicles from adult rats. The accumulation of 70 microM HMG by both newborn and adult tubules reached a steady state and achieved a distribution ratio (DR) of 4.9 and 6.5, respectively; decreased DR's at higher substrate concentrations suggest concentration-dependent uptake. Lineweaver-Burk analysis of the 5 min calculated velocities of HMG uptake by newborn and adult tubules indicate a single transport system with the same apparent Km of 0.2 mM in both age groups. The Vmax in adult rats was twofold greater than in newborn (0.95 versus 0.44 mM/1/5 min). The carrier system for HMG is assumed to be distinct from those of amino acids and sugars because tubule uptake of HMG is not affected by the presence of alpha-NH2-isobutyric acid and alpha-methyl-D-glucoside. Sodium maleate and acetoacetate significantly decreased HMG uptake in tubules of both age groups. HMG uptake by isolated renal brush border membrane vesicles from adult rats suggests that uptake is both carrier-mediated and Na+-dependent. These observations are consistent with renal tubular HMG uptake by an energy-dependent, carrier-mediated system.