In this issue of the Journal, Geisler and colleagues [1] report convincing epidemiologicalevidencethatcervicalinfection with Chlamydia trachomatis produces immunity in at least a subset of naturally infected women. Over a 2.5-year period, they enrolled 243 C. trachomatis–infected women in a treatment study. A standardized nucleic acid amplification test with high predictive value was used to document all infections. Two hundred women were seen in follow-up and constituted the study population. In the 1–7 week interval between when these women were first found infected with C. trachomatis and when they were seen in the followup for treatment, 44 (22%) had spontaneouslyclearedinfection.Allwomenwere treated with azithromycin 1 gm orally and scheduled for a subsequent visit approximately 6 months later. Thirty-three (17%) women were reinfected when seen in follow-up on average 183 days posttreatment. Strikingly, 31 (20%) of the 156 persistently positive women were reinfected, compared with only 2 (5%) of 44 women who spontaneously cleared infection (P= .02). This difference remained significant after controlling for age and treatment status of the reported sexual partner. This study provides the most convincing evidence yet that natural infection in humans engenders protective immunity. That said, immunity to C. trachomatis is clearly complex, and the mechanisms underlying immunity were not studied by Geisler et al. C. trachomatis is well suited for producing incomplete immunity. Its intracellular replication within epithelial cells shields it from antibody and T-cell attack. The replication cycle senses extracellular cytokines, and low concentrations of interferon gamma induce an aberrant, poorly replicating form of the organism that downregulates several of the protective antigens. Its major surface proteins demonstrate antigenic variation, either through allelic variation of the major outer membrane protein or phase variation of the polymorphic membrane proteins. In aggregate, these mechanisms probably delay the acquisition of immunity. Immunity in humans appears to take a long time to acquire. Molano et al [2]