The reappearance of syphilis as an important infectious disease in this country prompted a review of the methodology of diagnosis as viewed by the practitioner. Blind reliance on standard serologic tests for syphilis may be misleading. In our study, the disease, in various stages, was present in 24 patients whose serologic tests were negative. In 16, the negative test was the result of a positive prozone reaction, and the reagin became positive upon dilution of the serum. The newer treponemol tests (RPCF and TPI), darkfield and spinal fluid examinations were also valuable in establishing the diagnosis. The clinician must be aware of the possibility of active syphilis with a "false negative serology."