Cervical compliance increases dramatically at parturition in sheep independent of uterine activity. Recently, in vitro production of prostaglandin E2 (PGE2) by the cervix has been shown to increase at parturition. This study investigated the effects of PGE2 on cervical compliance and uterine blood flow in pregnant ewes. Eight animals were chronically instrumented with pressure balloons within the cervical os and amniotic cavity, an electromagnetic flow probe on a uterine artery, and catheters in the matermal cervical os, femoral artery, femoral, uterine, and cervical veins, and fetal hindlimb vein. PGE2 (10 mg) was administered in a water-soluble gel into the cervical os every 4 hours times three doses at least 5 days after surgical preparation (124 to 142 days' gestation). In all eight ewes, cervical compliance increased within 8 to 12 posttreatment hours to levels comparable to that seen at spontaneous parturition. Five of the ewes did not progress into labor; compliance in these ewes returned to baseline 24 to 72 hours after the peak. Uterine blood flow was measured in five ewes during the PGE2 treatment and demonstrated no significant alterations. Maternal cardiovascular and fetal respiratory parameters were monitored throughout the experiment and remained stable. The present data suggest that PGE2 may be an important regulator of the biochemical and physical changes which occur in the cervix at parturition.