An animal model of chronic cicatrizing trachoma has been produced by repeated ocular inoculation with Chlamydia trachomatis serotype E, a genitally transmitted strain. We have now produced a chronic follicular conjunctivitis on cynomolgus monkeys by repeated inoculation with C. trachomatis serotype A, which has been isolated from an area of endemic trachoma. This disease was similar in all respects to that which followed infection with the serotype E strain. Cynomolgus monkeys inoculated with a single dose of serotype E of C. trachomatis strain developed an acute, self-limited follicular conjunctivitis, which was intense for 4 weeks and then slowly subsided. The organism could be reisolated only during the first 4 weeks after inoculation. On reinoculation at 15 and 30 weeks after the initial infections, these animals demonstrated only a mild and transitory clinical response, and the agent could be recovered for only up to 14 days after inoculation. In contrast, repeated weekly reinoculation with either serotype led to a chronic progressive clinical response in these animals, although after the first 6 weeks the agent was isolated only occasionally. This chronic disease was shown not to be due to hypersensitivity to the egg yolk components in which the organism was grown. These data suggest that the serotype of the chlamydial organism may not be as important in determining the clinical course of disease as is the frequency or persistence of exposure to the chlamydial agent. Although a single inoculum produced an acute follicular conjunctivitis, repeated inoculation is needed to produce the chronic disease characteristic of trachoma in this animal model.