Standard therapy for Chlamydia trachomatis in the United States consists of a 7-day course of tetracycline administration. Recurrent infections are frequent, however, in circumstances in which reinfection seems unlikely, suggesting that the standard regimen may be insufficient to cure the infection. It may reduce the number of organisms, however, below a detectable level at a test-of-cure visit. To evaluate recurrent infection, the authors studied patients with chlamydia who were treated with standard therapy, and they found a recurrence rate of 29% among 2,983 patients who returned to the clinic during a 2-year follow-up period. Recurrent infection was associated with younger age but was not related to either race or gender. To test the hypothesis that a longer treatment course might be more effective in preventing recurrent infection, the authors conducted a randomized trial that compared 7- and 21-day regimens of tetracycline administration. Of the 918 subjects enrolled in the trial, 220 were infected with C. trachomatis. The overall recurrence rate among patients who were infected and returned was 18.4% (9/49) in the 21-day group and 13.8% (8/58) in the 7-day group (P = .60). Similar results were obtained using survival analysis methods. Given the number of subjects who returned, this study had approximately a 65% statistical power to detect a reduction in recurrence rate, from 20% to 5%. Because of the similarity of the results in the two groups, it was concluded that 21 days of tetracycline administration is no more effective in preventing recurrence than 7 days of administration.