Single-dose regimens of trimethoprim-sulfamethoxazole, amoxicillin and cyclacillin as treatment for acute cystitis were evaluated in 38 women. The trial was prematurely stopped because of frequent treatment failures. At 2 days after treatment, all 13 patients given trimethoprim-sulfamethoxazole were cured, while 4 (31%) of 13 given amoxicillin and 4 (33%) of 12 given cyclacillin had persistent bacteriuria. At 2 wk, 11 (85%) of 13 patients given trimethoprim-sulfamethoxazole, 6 (50%) of 12 given amoxicillin, and 3 (30%) of 10 given cyclacillin were cured. One patient with positive results of antibody-coated bacteria testing who was treated with cyclacillin had signs and symptoms of acute pyelonephritis 3 days after treatment, and 2 patients treated with amoxicillin and 1 treated with trimethoprim-sulfamethoxazole converted antibody-coated bacteria test results from negative to positive after therapy. Single-dose treatment of cystitis in unselected women with cyclacillin and amoxicillin may result in low cure rates and that progression to acute pyelonephritis may occur following ineffective single-dose therapy.