Although penicillin is the drug of choice in syphilis, treatment failures with benzathine and procaine penicillin have occurred in neurosyphilis. Patients allergic to penicillin have traditionally been treated with tetracycline but, since this drug diffuses poorly into the cerebrospinal fluid, its use in neurosyphilis is uncertain. In the case reported here, a penicillin allergic patient with general paresis of the insane was successfully treated with chloramphenicol. This drug has been used in the treatment of syphilis and achieves high concentrations in the cerebrospinal fluid. Thus chloramphenicol may be a more appropriate agent than tetracycline in treating patients with neurosyphilis who are allergic to penicillin.