Rectal infection with Chlamydia trachomatis affects approximately 7% of men having sex with men (MSM), attending departments of Genito-Urinary (GU) Medicine [Manavi et al. Int J STD AIDS 2004;15:162-4], and the British Association for Sexual Health and HIV (BASHH) guidelines for the treatment of uncomplicated genital C. trachomatis infection include 1 g of single-dose oral azithromycin as a recommended regimen [BASHH 2006]. A retrospective analysis was performed on case-notes from all patients diagnosed with rectal C. trachomatis infection in the department of GU Medicine, Edinburgh for the one-year period from 1 June 2005. Of 101 new episodes of rectal chlamydial infection, only 9% were associated with anorectal symptoms. Excluding these, 85% of asymptomatic patients were treated with a single dose of azithromycin 1 g orally, with a calculated treatment failure rate of 13% (nine of 68). This suggests that single-dose azithromycin may be a less than effective treatment in asymptomatic rectal C. trachomatis infection. The potential treatment failure rate with this regimen emphasizes the need for a test of cure at the appropriate interval following treatment to ensure clearance of infection.