We investigated the effects of 3 days treatment with acetazolamide 250 mg three times daily on kidney function in 8 Type 1 (insulin-dependent) diabetic patients with nephropathy, and in 7 healthy subjects in a double-blind placebo controlled cross-over study. Glomerular filtration rate and extracellular fluid volume were measured with the single injection 51Cr-EDTA technique and fluid flow rate from the proximal tubules was determined by measurement of the renal lithium clearance. A 24% decline in glomerular filtration rate was observed in both groups during acetazolamide treatment (control subjects: 108 +/- 11 vs 82 +/- 9 ml/min, p less than 0.02, diabetic patients: 71 +/- 19 vs 54 +/- 14 ml/min, p less than 0.01). The renal lithium clearance (ml/min) remained about the same (control subjects: 22 +/- 6 vs 27 +/- 8, NS, diabetic patients: 14 +/- 5 vs 15 +/- 4, NS). Absolute proximal tubular reabsorption of water (ml/min) was reduced by about one-third (control subjects: 85 +/- 11 vs 56 +/- 7, p less than 0.02, diabetic patients: 55 +/- 17 vs 37 +/- 6, p less than 0.02), and fractional proximal reabsorption of water and sodium (%) declined (control subjects: 79 +/- 5 vs 67 +/- 8, p less than 0.02, diabetic patients: 79 +/- 5 vs 72 +/- 6, p less than 0.02). Renal sodium clearance and distal fractional reabsorption of sodium was unchanged. Extracellular fluid volume declined by 10% in both groups (p less than 0.02). Albuminuria and fractional albumin clearance decreased significantly in the nephropathic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)