Five patients with laboratory evidence of latent or neurosyphilis were treated orally with doxycycline (200 mg) twice a day for 21 days. After the seventh dose, the mean level of doxycycline in serum was 5.8 micrograms/ml, with a mean drug level in cerebrospinal fluid of 1.3 micrograms/ml. The mean penetration into cerebrospinal fluid was 26%. These preliminary findings suggest that doxycycline, administered orally at a dose of 200 mg twice a day, reaches a sufficient concentration in cerebrospinal fluid to be worthy of further evaluation as an alternative regimen to penicillin therapy for latent or neurosyphilis.