Interleukin-8 (IL-8) is a cytokine that induces selective neutrophil chemotaxis and activation. Progesterone inhibits and antiprogestins stimulate production of IL-8 by chorion and decidua. Cervical ripening is associated with an influx of inflammatory cells into the cervix, but the role of IL-8 in primate parturition remains to be established. To investigate the role of IL-8 in cervical ripening, we administered purified, human fibroblast-derived IL-8 intravaginally to 3 pregnant monkeys beginning at 137-139 days of gestation (term = 167 days) at a dose of 150 ng/kg. The cervix was evaluated by a modified Bishop's Score. IL-8 was administered in vehicle (2.5% hydroxypropyl cellulose [HPC] with 300 fl Evans Blue solution) by inserting a 1.0 or 3.0 ml syringe into the vaginal vault. Amniocentesis was performed at intervals to determine changes in amniotic fluid prostaglandins and cytokines. After a recovery period of 4-5 days, a second dose of IL-8 (300 ng/kg) was administered. The effect of graded doses of intravaginal IL-8 on modified Bishop's Scores (mean q SEM) Dose 0 hours 24 hours 48 hours 72 hours 150 ng/kg 0.6 q 0.3 5.6 q 0.3* 5.0 q 1.2* 5.3 q 0.3* 300 ng/kg 2.0 q 1.0 4.0 q 3.0 6.5 q 0.5* * different from time 0 hrs at P<0.05 (t-test). Two out of three animals showed an increase in amniotic fluid IL-8 concentrations but there were no changes in amniotic fluid PGE2 or PGF2`. One animal delivered after the second dose of IL-8. Intravaginal application of purified human fibroblast-derived IL-8 induces significant cervical ripening in late pregnant rhesus monkeys. This data may have important implications in therapies related to induction of cervical ripening and labor.