OBJECTIVE: Preterm birth (PTB) is the leading cause of perinatal mortality and morbidity in industrialized nations. Although numerous risk factors for PTB have been identified, PTB frequently occurs in women with no known risk factors, suggesting additional influences. Since the placenta, which is largely a paternally derived organ, is critical to successful pregnancy, we examined the potential contribution of paternal dioxin exposure on the incidence of PTB in an otherwise healthy female. DESIGN: Laboratory based study. MATERIALS AND METHODS: Pregnant mice were given the environmental toxicant dioxin (10 ug/kg) on gestation day 15 (E15). Adult male offspring (F1) and unexposed males (controls) were mated with unexposed females. Pregnant females were monitored to observe gestation length or sacrificed on E18 for histological examination of placental/decidual units, cervices, and ovaries. RESULTS: All females mated to unexposed males delivered at term (E20) while 35% of females mated to F1 males exposed to dioxin delivered 24-36 hours early. Histological assessment of control placental/decidual units displayed a clear distinction between the labyrinthine, junctional, and decidual zones and abundant progesterone receptor (PR) while units from F1 males were highly disordered and exhibited alterations in collagen deposition and diminished PR. Histological examination of the ovaries and cervices by caspase-3 and Muc1, respectively, revealed normal ovaries with minimal evidence of luteolysis in females mated to unexposed males. Cervices from these animals displayed limited mucous production, indicating minimal cervical ripening. In contrast, females mated to F1 males displayed ovaries with evidence of luteolysis and cervical ripening was also evident. CONCLUSION: Our study provides evidence that paternal exposure to a common environmental toxicant may represent a previously unrecognized risk for PTB.