We evaluated the cost-effectiveness of screening women at moderate (prevalence, 7.9%) risk for urogenital infections with Chlamydia trachomatis. The characteristics of culture and direct antigen tests were based on published values. Those of serology were based on a comparative study in 434 college women. Three serological tests were evaluated: microimmunofluorescence, an indirect fluorescent antibody assay, and an enzyme-linked immunoassay. Their sensitivities and specificities were 97% and 64%, 87% and 64%, and 84% and 51%, respectively, compared with culture. Screening all patients with a direct antigen test costing less than $12 was more cost-effective than neither testing nor treating patients, although only 53% of patients with positive test results would actually be infected. The use of culture alone or as a confirmatory test was less cost-effective but had high positive predictive values. Seropositivity was not highly predictive of active infection. Chlamydial screening can be cost-effective in moderate-risk women.