Sulfonamides, trimethoprim-sulfamethoxazole, nitrofurantoin, and nalidixic acid are excreted in the urine in high concentration and, with the exception of Pseudomonas aeruginosa and Serratia marcescens, are all active in vitro against usual aerobic gram-negative bacteria. They are useful for treatment of uncomplicated lower urinary tract infections in an outpatient setting but are probably not indicated for acute upper tract infections, especially in the hospitalized patient. Trimethoprim-sulfamethoxazole is a very effective combination agent in vitro, has appealing pharmacokinetic properties, and is usually well tolerated by patients. However, it is more expensive than the sulfonamides and is ordinarily not indicated for initial treatment. A sulfonamide is in our view still the agent of first choice, with either nitrofurantoin or nalidixic acid as an alternative if sulfonamides cannot be tolerated.