We propose that generation of reactive oxygen species may be a potentially reversible pathophysiologic pathway leading to preterm premature rupture of the membranes. Reactive oxygen species generated by the body's response to diverse insults such as infection, cigarette smoking, bleeding, or cocaine use can activate collagenolytic enzymes and impair fetal membrane integrity. Vitamin E, a lipid-soluble antioxidant, inhibits membrane-damaging effects of reactive oxygen species-induced lipid peroxidation. Vitamin C, a water-soluble antioxidant in plasma, stimulates and protects collagen synthesis while recycling vitamin E. Prior evidence shows that (1) damage by reactive oxygen species can impair fetal membrane integrity, (2) reduced midgestation levels of vitamin C are associated with preterm premature rupture of membranes, and (3) these vitamins can be safely and effectively absorbed and delivered to gestational tissues. Current prenatal vitamin preparations contain vitamins C and E in concentrations that are less than 1/3 and 1/10, respectively; these levels have been suggested for effective antioxidant protection. We hypothesize that increased dietary consumption or supplementation of vitamins C and E during pregnancy may reduce physiologically the risks of that portion of preterm premature rupture of membranes that is mediated by excessive or undamped peroxidation of fetal membranes. This hypothesis, if confirmed, should stimulate initiation of therapeutic trials to test the efficacy of enhanced supplementation with vitamins C and E during pregnancy to prevent preterm premature rupture of membranes.