Treponemes may persist after treatment that has been accepted as effective; the reasons for this are discussed. Nevertheless, the epidemic of syphilis after the second world war was not followed by an epidemic of late syphilis, and the results of treatment with penicillin are excellent. Neurological signs may progress in some treated patients, and the standard doses of soluble penicillin and any dose of benzathine penicillin (even with added probenecid by mouth) cannot be relied on to achieve treponemicidal concentrations in the cerebrospinal fluid (CSF). There are no large scale studies of CSF findings after treatment of early syphilis with benzathine penicillin. Standard dosage, such as procaine penicillin G 600 000 international units (IU) by intramuscular injection for 10 days, is the treatment of choice for the patient suffering from uncomplicated early syphilis; this should be preferred to benzathine penicillin, which should only be used when standard treatment as above cannot be given. Treponemicidal concentrations of penicillin should be achieved in the CSF of patients suffering from neurosyphilis by schedules of probenecid by mouth and procaine penicillin by single daily intramuscular injections; treatment should last for 17 to 21 days. Benzathine penicillin should not be used for the treatment of patients suffering from neurosyphilis or from the iritis of late syphilis including that accompanying interstitial keratitis. Treatment for interstitial keratitis should initially be as for neurosyphilis, but in recurrent cases it may have to be prolonged to eradicate Treponema pallidum that is dividing slowly. Doxycycline 200 mg by mouth daily for 21 days provides a supervisable outpatient schedule for patients allergic to penicillin. Cephaloridine (and probably cefuroxime and the new cephalosporins) may be useful for patients who are allergic to penicillin but have not developed anaphylactic allergy. If erythromycin is used for treating syphilis in pregnant women who are allergic to penicillin, then the newborn babies should be treated with penicillin.