Fetal syphilis is the presumed diagnosis when the sonographic findings of fetal hydrops are found in the presence of maternal syphilis. In the absence of fetal hydrops, the diagnosis of fetal infection is difficult. We hypothesized that intra-amniotic infection would be accompanied by anatomic placental and fetal abnormalities that could be detected by ultrasonography. Rabbit infectivity testing (RIT), intratesticular inoculation of rabbits with amniotic fluid, can be used to confirm intra-amniotic infection with Treponema pallidum. Twenty-one gravidas with untreated early (primary, secondary, and early latent) syphilis underwent sonography and amniocentesis for RIT at 24 weeks of gestation or later. Antenatal sonographic findings were compared to their amniotic fluid RIT results. Hepatomegaly was significantly (P < 0.01) associated with amniotic fluid infection detected by RIT. Antenatal detection of hepatomegaly, which is probably the initial sonographic manifestation of hydrops fetalis, may ultimately identify the fetus affected with congenital syphilis.