We compared 7-day regimens of ciprofloxacin in dosages of 750 and 1000 mg twice daily with doxycycline 100 mg twice daily for the treatment of nongonococcal urethritis in 178 men enrolled in a prospective, randomized, double-blind trial. The overall clinical response was comparable in the three treatment groups at both 2 and 4 weeks after therapy. However, among patients who initially had cultures positive for chlamydia, Chlamydia trachomatis was reisolated within 4 weeks after treatment in none of 10 doxycycline-treated patients, in 11 (52%) of 21 patients treated with 750 mg of ciprofloxacin twice daily, and in six (38%) of 16 patients treated with 1000 mg of ciprofloxacin twice daily. Each of the recurrent strains was identical in serotype to the original infecting strain. We conclude that ciprofloxacin in dosages as high as 2 g daily is inadequate for treatment of chlamydial urethritis in men, often resulting in relapsing infections.