To examine bicarbonate reabsorption at different GFR's, we varied the renal perfusion pressure in anesthetized dogs after inhibiting autoregulation by expanding extracellular volume and infusing ethacrynic acid. At a plasma bicarbonate concentration (PHCO3) of 28 +/- 1 mM, bicarbonate reabsorption varied in proportion to GFR (glomerulotubular balance). When PHCO3 was raised to 52 +/- 2 mM at constant PCO2 and hematocrit, bicarbonate reabsorption was reduced at all levels of filtered load. When plotted against GFR, different results were obtained dependent on the GFR level examined. At the control GFR,. bicarbonate loading reduced bicarbonate reabsorption by 30 +/- 5%. At a GFR level about 50% below the control GFR, bicarbonate loading increased reabsorption by about one third because the inhibitory effect of raising PHCO3 and extracellular pH was not sufficient to counteract the stimulatory effect of a higher filtered load. At intermediate levels of GFR, a rise in PHCO3 did not alter bicarbonate reabsorption. The finding that acetazolamide (30 mg/kg of body wt) at high PHCO3 failed to reduce bicarbonate reabsorption supports the hypothesis that the depressive effect of high extracellular pH on bicarbonate reabsorption may be attributed to reduced net tubular hydrogen ion secretion.