Azithromycin 1 g immediately and doxycycline 100 mg twice daily have good antimicrobial activity against Chlamydia trachomatis and treatment studies have demonstrated a >95% microbiological cure at 2–5 weeks, with antimicrobial resistance being rarely reported. Recently an 8% (95%, CI 5% to 11%) failure rate was observed in 289 women, but not in men, who had been sexually inactive after treatment. At high multiplicities of infection (load) in vitro persistence can often be demonstrated to antimicrobials—heterotypic resistance. The subsequently recovered isolates do not possess antimicrobial resistance at low loads. It is known that genital chlamydia load varies in vivo and is probably greater in women than men. In mass treatment trials of trachoma, treatment failure is associated with high chlamydia loads. It is therefore possible that women with high chlamydia loads may be at increased risk of treatment failure. Given the imminent role out of the National Chlamydia Screening Programme and the consequences of persistent chlamydial infection in women this hypothesis urgently merits further investigation.