The effect of co-trimoxazole on creatinine clearance was studied in six individuals with normal kidney function. The mean decrease in creatinine clearance during treatment was 47 ml/min and the mean increase in plasma-creatinine was 0.27 mg/dl (P less than 0.01). Although creatinine clearance decreased by 29%, sodium excretion increased by 22%. Discontinuation of co-trimoxazole resulted in a prompt return of creatinine clearance to pretreatment values, and a consistent antinatriuresis.