There is compelling evidence that trachoma-inclusion conjunctivitis (TRIC) agents can and do persist in clinically "healed" subjects, raising the possibility that such persistent cases may constitute reservoirs of infection. The percentage of persistent cases, with antigen detection utilizing polymerase chain reaction, ligase chain reaction, or Giemsa stain techniques, varies from 24% to 53%. The hypothesis put forth in this review is that persistent antigens can cause the endogenous reactivation of clinical disease after being triggered by factors that cannot be clearly elucidated at the present time. Based on the findings of existing studies, it is not evident at this time if single-dose azithromycin will eradicate persistent infection and prevent reactivation through this pathway. Repeat cycles of infection are probably, in large part, caused by this endogenous reactivation, which leads to conjunctival scarring/shrinkage and entropion/trichiasis. The evolution of trachoma from incipient to healed stages, coupled with the infection, reinfection and reactivation cycles, and the interaction of these cycles and stages with environmental factors, compels the postulation of a trachoma ecosystem in which all these factors are integrated.