Penicillin G or ampicillin was administered orally to 144 dogs with urinary tract infections. The daily dosage of penicillin G ranged from 110,000 to 165,000 U/kg (50,000-75,000 U/lb), and the dosage of ampicillin varied from 77 to 110 mg/kg (35-50 mg/lb). The daily dose of each antibiotic was divided into 3 or 4 doses and given at approximately 8- or 6-hour intervals for 10 to 14 days. Response to treatment, based on results of urine culture, varied from no response for infections caused by Pseudomonas spp to 100% response for those caused by Staphylococcus aureus and Streptococcus spp. About 50% of infections caused by Escherichia coli were eliminated, as were about 80% of those due to Proteus mirabilis. Mean concentrations of penicillin G and ampicillin in urines collected at 6-hour intervals after oral administration to clinically normal adult dogs were approximately 350 microgram/ml for both drugs when each was given individually in daily dosages (divided QID) of 55 mg/kg (25 mg/lb). The minimum inhibitory concentration of penicillin G for a number of the bacteria isolated from the urine of the infected dogs was compared with the results of the clinical trials and to the minimum inhibitory concentration of a larger number of urinary bacterial isolates.