The mechanism of excretion of nitrofurantoin in the kidney was studied in anesthetized dogs by direct collection of urine from ureteral catheters. The method of stop flow analysis, involving a period of occlusion of the ureter, was applied in order to determine in which part of the nephron nitrofurantoin is excreted; in addition, simultaneous nitrofurantoin and creatinine clearance determinations were performed on four dogs at varying levels of urinary pH and plasma CO2combining power. The results showed that nitrofurantoin is handled by glomerular filtration and tubular reabsorption. Tubular reabsorption was greater when the urine was acid. Alkalinizing the urine resulted in higher nitrofurantoin concentrations in the urine and less tubular reabsorption.