We evaluated the ability of the urinary leukocyte esterase test to predict culture-verified chlamydial and gonococcal urethritis among asymptomatic adolescent males. Nine hundred forty-eight sexually active males provided first-catch urine samples for esterase screening, and 76 (8%) tested positive (greater than or equal to 1+). Among 435 boys who agreed to undergo urethral culture, the esterase was positive in 66 (15%), Chlamydia trachomatis was isolated from 39 (9%), and Neisseria gonorrhoeae was isolated from 14 (3%). The sensitivity, specificity, and positive and negative predictive values for the esterase test were 72%, 93%, and 58% and 96%, respectively. Using the esterase test to screen asymptomatic males for urethritis, we identified 38 culture-verified infections that otherwise would have remained undetected. The urinary leukocyte esterase test is a noninvasive and cost-effective screening method to detect urethritis among asymptomatic adolescent males.