This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically iv, would increase tubular sodium reabsorption and cause hypertension. Glucose (G) was infused for 6 days (14 mg/kg/min, iv) in 5 uninephrectomized (UNX) dogs. MAP and renal blood flow (RBF) were measured 18 hrs/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6-days, coupled with a significant, sustained increase in RBF, averaging approximately 20% above control on day 6. GFR and PRA also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in 6 dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was prior to the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offset any potential renal actions to increase MAP in this experimental model in dogs.