Maternal infection with syphilis can result in focal areas of vasculitis and, similarly, placental villitis and obliterative arteritis. We hypothesized that Doppler systolic-diastolic ratios (S/Ds) in pregnancies complicated by maternal syphilis infection might reflect an increased resistance to placental perfusion. Doppler velocity waveform analysis was used to study the uterine and umbilical arteries in third-trimester pregnancies complicated by maternal syphilis infection. A control group of similarly studied normal pregnancies was used for comparison. Statistically significant increases were found in the mean S/Ds of both the uterine and umbilical arteries in the syphilis group compared with the normal group, indicating an increased resistance to perfusion of the placenta in pregnancies complicated by syphilis. This difference was even greater in association with the identification of spirochetes in the amniotic fluid by dark-field microscopy, indicating that the S/D results are related to the presence of intrauterine infection. Serial S/Ds in a small subgroup of patients correlated with the clinical courses, including an apparent acute vascular-resistance change associated with treatment, probably due to the Jarisch-Herxheimer reaction. Because of these post-treatment vascular events, the pre-treatment S/D alone may have a limited clinical predictive value for treatment efficacy in congenital syphilis.