The possibility of gender differences in the relationship between dose and efficacy of drugs has historically been limited. The aim of the present study was to evaluate the influence of sex on the pharmacodynamics of furosemide (FUR) in adult Wistar rats. Conventional renal clearance studies were performed in the absence and in the presence of a FUR dose necessary to produce identical urine excretion rates of FUR in both sexes. Fractional excretions of sodium, potassium, and water were similar in male and female rats in the absence of FUR. Natriuretic, kaliuretic, and diuretic responses to FUR, when expressed in fractional terms, were significantly increased in female rats. Diuretic, natriuretic, and kaliuretic efficiencies of FUR were also higher in female rats as compared with males. This might be explained by the lower abundance of the Na-K-2Cl cotransporter observed in homogenates from the medullae of female kidneys as compared with male ones.