Previous work has suggested that co-trimoxazole may be superior to trimethoprim in the treatment of complicated urinary tract infection. A prospective study has been done to assess the relative value of the drugs in this situation using trimethoprim at higher than normal dosage. Fifty three patients (33 women and 20 men) were randomly allocated to either a fourteen-day course of co-trimoxazole tabs, 2 twice a day (27 patients) or trimethoprim 250 mg twice a day (26 patients). After patient withdrawals from the study, 17 (77%) of the co-trimoxazole group achieved a sterile urine three weeks after starting treatment compared with 15 (65%) in the trimethoprim group (X2 = 0.80). When those patients with sterile urine at three weeks who could be reassessed four weeks later were analyzed, 8 (89%) of the co-trimoxazole patients maintained a sterile urine against 7 (58%) in the trimethoprim group (X2 = 1.09). Although statistical significance was not attained, the results suggest that even at increased dosage, trimethoprim would not appear to be as efficient as co-trimoxazole in complicated urinary tract infection.