We found inflammatory patterns of transparent lymphocytes on increased numbers of histiocytes suggestive of chlamydial infection in 68 (56%) of 121 cervical cytologic smears. Chlamydia trachomatis was isolated from 36 (53%) of those with and only two (4%) of those without such inflammatory patterns. Direct stain with fluorescein-conjugated monoclonal antibodies demonstrated elementary bodies of C trachomatis in 30 (79%) of the 38 culture-positive patients, including 29 of the culture-positive patients who had an inflammatory cytologic pattern suggestive of C trachomatis infection. Thus, Papanicolaou smears can be screened for inflammatory pattern, and separate endocervical smears from patients with a pattern suggestive of chlamydial infection can then be stained by immunofluorescence to confirm the presence of C trachomatis infection. This two-step approach detected 29 of 38 infections confirmed by culture in the present study, giving a sensitivity of 76%, a specificity of 100%, and a positive predictive value of 100% in a population having a 31% prevalence of C trachomatis infection.