Four patients (three men, 32, 43, and 53 years old, and one 37-year-old woman) with syphilitic neuroretinitis had cerebrospinal fluid evidence of neurosyphilis. Therapy failed in one patient given penicillin G benzathine intramuscularly and it may have failed in a second patient. Another treatment failure occurred in a patient given tetracycline orally. Intramuscular penicillin G benzathine or intramuscular penicillin G procaine in doses of less than 2.4 million units/day does not produce spirocheticidal drug levels in the cerebrospinal fluid. All four patients improved after high-dose treatment with aqueous penicillin G.