Prematurity is the leading cause of perinatal mortality in the United States. Intrauterine infection is thought to be an important cause of premature labor and delivery. We have previously demonstrated that experimental intraamniotic infection in rhesus monkeys leads to sequential increases in amniotic fluid cytokines (TNF`, IL-1 ) and prostaglandins (PGE2 and PGF2`), followed by preterm labor and delivery. To characterize the temporal sequence of events following choriodecidual infection, we utilized chronically instrumented rhesus monkeys with timed gestations in which choriodecidual infection was established by inoculation of either low inoculum (<103 cfu) or high inoculum (>104 cfu) Group B streptococcus (GBS) into the choriodecidual space. Following infection, labor occurred in 1 of 3 low inoculum and in 3 of 4 high inoculum animals (P<0.05). In other animals with infection-induced labor, increases in uterine contractility occurred 25 hours (14-50 hrs) after inoculation, and in all cases was preceded by intraamniotic invasion by the GBS by 13 hours (6-18 hrs). Following, but not preceding intraamniotic recovery of GBS, significant increases in amniotic fluid cytokines and in PGE2 occurred Median Amniotic Fluid Concentrations (pg/ml) Event TNF` IL-1 PGE2 PGF2` Pre-inoculation 50 <20 262 158 Onset Labor 1,600 1,120 7,749 241 These data demonstrate that choriodecidual infection may ascend to the amniotic cavity, and that following the establishment of intraamniotic infection, leads to preterm labor. In contrast, choriodecidual infection did not lead to preterm labor without concurrent intraamniotic infection.