Glomerular filtration rate, urine flow, and Na excretion were measured 3--4 h after unilateral nephrectomy (1/2Nex) or sham operation in unanesthetized rats infused with isotonic saline (0.05--0.75 ml/min) and additionally injected with acetazolamind (20 mg/kg i.p.) or furosemide (5 mg/kg i.p., or 0.2 mg/kg i.v., or 2.0 mg/kg i.v.) or with both agents. Glomerular filtration rate of unilaterally nephrectomized rats averaged 50% of controls. Under all experimental conditions investigated, absolute water and Na excretions were similar in 1/2Nex and sham-operated rats. The fractional excretion (FE) of water and Na was increased 1.5- to 2.2-fold in 1/2Nex animals. The diuretic effects of volume expansion, of the two diuretic agents, and of contralateral nephrectomy consistently were additive. The "compensatory" increase of FESa following contralateral nephrectomy entailed a proportional increase of the diuretic effects of agents given subsequently. Urinary furosemide excretion 15 min after intravenous injection in unilaterally nephrectomized rats was smaller than in controls. The additivity of the diuretic effects of contralateral nephrectomy ("compensatory adaptation") and volume expansion and/or diuretic agents appears to be partly explained by different sites of action.