Certain advantages might accrue to the use of sulfonamides such as sulfamerazine (2-sulfonamido 4-methyl pyrimidine) that, having essentially the same antibacterial activity as others in common use, are characterized by low rates of renal excretion ( 1 to 6). These advantages include lower and less frequent dosage and, perhaps, some reduction of the renal hazard incidental to the precipitation of material in the kidneys and urinary tract. It was because of these considerations that it was deemed advisable to study some of the factors concerned with the excretion of sulfamerazine. Observations were also made on the excretion of the N'-acetyl derivative of sulfamerazine and of sulfadiazine (2-sulfanilamido pyrimidine) for comparative purposes.The study was conducted in a manner that yields quantitative information on the various discrete processes involved. This was accomplished by the simultaneous measurement of the renal plasma clearance of the drug and the rate of glomerular filtration under different experimental conditions.Measurements were also made on the extent to which sulfamerazine is bound to the non-diffusable constituents of plasma, presumably plasma albumin, since it is only the unbound drug in the plasma water that is presented to the glomeruli for filtration. The ratio of the unbound drug clearance to the concurrent rate of glomerular filtration (excretion ratio) yields information on the extent to which the filtered material is reabsorbed or excreted by the renal tubules. The dog experiments were performed on 3 well-trained female mongrels. The glomerular filtration rate was measured by the creatinine clearance (8). The sulfamerazine clearance and glomerular filtration rate were determined simultaneously for several collection periods. Various procedures designed to alter the excretion of the drug were then introduced and the observations continued.Blood was obtained during each experiment for the estimation of total plasma protein and albumin content so that the concentration of unbound sulfonamide in the plasma water could be determined and its clearance calculated. The proportion of total plasma sulfonamide bound on the non-diffusible constituents of plasma was determined by dialysis across a cellophane membrane against an isotonic phosphate buffer at pH 7.4 and 370 C.Eighteen hours were allowed for the establishment of an equilibrium. All values for plasma binding were corrected to a standard plasma albumin content of 4.0 grams per 100 ml. This correction assumes that the plasma albumins of different individuals have no qualitative differences in their abilities to bind sulfonamides. Each experiment was performed in duplicate, at 4 different concentrations of plasma sulfonamide.Chemical methods. The concentration of mannitol in the plasma and urine was determined by a modification (9) of (7); creatinine by a modified Folin procedure on tungstic acid filtrates (10); and sulfonamides by the method of (11). Twenty per cent p-toluene sulfonic acid was used as the precipitating and hydrolyzing agen...