Interleukin-1 has been postulated as a signal for the initiation of preterm labor and delivery. Interleukin-1 is produced by human decidua, stimulates prostaglandin production by intrauterine tissues, and is present in the amniotic fluid of women with preterm labor and intraamniotic infection. The purpose of these studies was to determine whether interleukin-1 could induce parturition in an animal species. Timed-pregnant C3H/HeJ inbred mice (n = 24) (genetically endotoxin resistant) were randomized to receive either recombinant human interleukin-1 or sterile phosphate-buffered saline solution between days 15 and 17 of gestation (normal length of pregnancy, 20 to 21 days). Three consecutive subcutaneous injections of interleukin-1 or phosphate-buffered saline solution were administered within 6 hours. Examinations of the animals were performed by blinded observers. Parturition occurred within 24 hours in all of the interleukin-1-treated mice and in none of the control group. Vaginal bleeding was first noted 4 hours after the first interleukin-1 injection, and delivery began within 12 hours after the last interleukin-1 injection. Premature delivery occurred in all interleukin-1-injected mice. Laparotomy revealed that there were no remaining fetuses in utero. All mice in the control group delivered spontaneously between days 20 and 22. We conclude that systemic administration of interleukin-1 induces preterm labor and delivery in mice.