Although a diminished fractional excretion of sodium (FENa) is the hallmark of acute proliferative glomerulonephritis (APGN), an enhanced natriuresis per glomerular filtration rate (GFR) in the chronic phases of this disease has been reported. We studied this adaptive response utilizing two different split-bladder dog models with unilateral, and a third group of dogs with bilateral Masugi's nephritis. Group I. Six dogs with unilateral nonaccelerated APGN studied a mean of 6 days after induction had a mean base-line APGN/intact kidney GFR of 31/50 ml/min (P less than 0.005) and FENa of 0.2/0.75% (P less than 0.005). Acute volume expansion caused a smaller absolute increase in FENa from the APGN kidney, 1.6%, than from the intact kidney, 4.0%, (P less than 0.01). Maximum tubular secretion of rho-aminohippuric acid/GFR (TmPAH/GFR) measured in three dogs was higher in the APGN kidney than intact kidney, 13.1 vs. 9.3 mg/dl. Subsequent studies on three of the six dogs when the disease had become chronic demonstrated a reversal in the pattern of sodium excretion in response to volume expansion. Group II. Six dogs with accelerated unilateral APGN (dogs presensitized to antibody source) studied a mean of 5 days after induction had a mean base-line APGN/intact kidney GFR of 16/57 ml/min and FENa of 0.22/0.12% (P less than 0.1). Contrary to group I, volume expansion caused a greater absolute increase in FENa from the APGN kidney, 5.8%, than from the intact kidney, 2.9% (P less than 0.05). TmPAH/GFR studied in four dogs was similar for both kidneys, 17.9 and 18.5 mg/dl for the APGN kidney and intact kidney, respectively. Group III. Sequential studies were performed on seven dogs with bilateral nonaccelerated APGN. Initially each demonstrated sodium retention and a smaller absolute increase in FENa in response to volume expansion compared to a predisease control study. With disease progression, volume expansion induced a greater absolute increase in FENa than in the control study. We concluded that (a) the fractional excretion of sodium from the APGN kidney will be less or greater than the contralateral intact kidney or control study depending on the severity and/or chronicity of the disease, possibly as the result of morphologic alterations; (b) the degree of extracellular fluid volume expansion is an important variable influencing similarity of glomerulotubular balance between the APGN and contralateral intact kidney; and (c) the "intact nephron hypothesis" applies in a limited fashion to kidneys with APGN in the absence of volume expansion just as it does for kidneys with chronic glomerulonephritis or pyelonephritis.