The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl-transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (r = 0.755; p < 0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary gamma-GTP activity in the patients did not differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r = -0.721; p < 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the extensive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.