In the present study, 8 Type 1 diabetic patients with normal creatinine clearance and 8 matched controls were examined. Tamm Horsfall glycoprotein was isolated with the NaCl precipitation procedure. Its purity was checked by gel-electrophoresis, immunodiffusion and isoelectric focussing. Tamm Horsfall glycoprotein of diabetic patients had higher glucose (p less than 0.05) and lower N-acetylneuraminic acid content (p less than 0.01) than controls. 14C-furosemide binding by Tamm Horsfall glycoprotein was examined using an Amicon ultrafiltration system at 0 degree C. In nominally sodium-free medium, furosemide binding by Tamm Horsfall glycoprotein was significantly (p less than 0.01) higher in diabetic patients than in matched controls. The increment of binding capacity with sodium was similar in controls and diabetic patients so that maximal binding capacity in a NaCl system was 1.7 +/- 0.3 in controls and 3.64 +/- 0.5 in diabetic patients (p less than 0.025). Half maximal furosemide binding by Tamm Horsfall glycoprotein occurred at 1.4 +/- 0.2 mmol Na/l in controls and 0.52 +/- 0.12 in diabetic patients (p less than 0.01). Abnormal radiofurosemide binding of Tamm Horsfall glycoprotein of diabetic patients may be the consequence of abnormal postribosomal modification of the glycoprotein which is synthesized in an insulin- and glucose-sensitive nephron segment.