Thirty-three gravidas with syphilis were monitored with hourly vital signs and examinations for 24 hours after treatment with benzathine penicillin G. Fifteen (45%) of the subjects had a Jarisch-Herxheimer reaction, including all three, 12 of 20 (60%), and none of ten of those with primary, secondary, and latent syphilis, respectively. The most common symptoms were fever (73%), uterine contractions (67%), and decreased fetal movement (67%). The signs or symptoms began 2-8 hours after treatment; fevers peaked at 6-12 hours post-therapy and the events usually abated by 16-24 hours after treatment. Uterine contractions and decreased fetal activity began concurrent with maternal fever in eight of ten women reporting contractions. Transient late decelerations were detected in three of 11 monitored patients. Three of the women with Jarisch-Herxheimer reactions delivered infants with congenital syphilis, including one stillbirth, but none of those without a detectable reaction had fetal treatment failures. Prostaglandin F2 alpha and prostacyclin metabolites were elevated transiently in the one subject studied, suggesting their role in mediating the cardiovascular and uterine events in the post-treatment period. The Jarisch-Herxheimer reaction in pregnancy is similar in frequency, character, and intensity to that in nonpregnant adults, but gravidas may have increase uterine activity and transient alterations in fetal well-being. The pregnant patient with a severely affected fetus with congenital syphilis may experience preterm labor, preterm delivery, or fetal death in association with the Jarisch-Herxheimer reaction.