To characterize the problem of unsuspected Chlamydia trachomatis infection in heterosexual men attending a sexually transmitted diseases (STD) clinic, the authors assessed risk factors for infection and the value of screening for infection by gram-stained smears and urinalysis in 438 men who did not have conventional clinical indications for chlamydial treatment at their initial visit. Evaluations included urethral swabs for gram-stained smears and Neisseria gonorrhoeae and C. trachomatis cultures and microscopy of first-catch urine sediment. C. trachomatis was isolated from 29 subjects (6.6%) and N. gonorrhoeae from 6 subjects (1.3%), (P less than .05). The only demographic or clinical factors that were associated with C. trachomatis were age younger than 21 years and five or more lifetime sexual partners. Screening for C. trachomatis with urethral gram stain and urine sediment examination had sensitivities of only 23% and 35%, respectively. Risk factor assessment and screening with standard microscopic procedures do not adequately predict infection in this group, which accounts for almost 25% of the C. trachomatis burden in heterosexual men who visit an STD clinic. More specific chlamydia detection methods are needed for effective control programs.