Background and Objectives: To evaluate the potential yield of routine serologic testing for syphilis in hospitalized patients. Study Design: Sera from consecutive patients admitted to an inpatient general medical service of a Baltimore hospital were tested using the RPR and FTA-ABS tests for syphilis. Two hundred ninety-one (149 males and 142 females) of 344 patients (85%) hospitalized during the study period participated, with ages ranging from 17 to 98 years. Seventy-seven percent of participants were African-American. Results of serologic tests for syphilis and human immunodeficiency virus were correlated with questionnaire responses. Associations were sought between results of serologic testing and demographic characteristics, medical problems, and a history of syphilis. Results: No patient had an admitting diagnosis of syphilis. Thirty-seven patients (13%) had both reactive RPR and FTA-ABS tests. Although serologic evidence of syphilis was significantly associated with age older than 50 years and with a history of syphilis, 59% of patients with both reactive RPR and FTA-ABS tests did not give a history of syphilis. Ten percent of patients were HIV seropositive; however HIV seropositivity was not significantly associated with serologic evidence of syphilis. Conclusion: Unsuspected latent syphilis was common in this population. Routine serologic screening for syphilis shoul. © 1994 American Sexually Transmitted Diseases Association.