OBJECTIVE Meconium passage with pulmonary aspiration in utero is associated with surfactant inactivation and is a major cause of neonatal morbidity and mortality. Ventilation with low surface tension perfluorocarbon in animal models of meconium aspiration has been shown to improve both oxygenation and lung compliance. Exogenously administered surfactant is inactivated by meconium. We wished to determine whether meconium would alter the surface properties of perfluorooctyl bromide (perflubron). METHODS Biophysical analysis using novel methods. METHODS University research laboratory. METHODS Healthy newborns. METHODS First pass meconium was obtained from healthy newborns. RESULTS We evaluated the surface-active properties of perflubron after exposure to meconium-saline dilutions using the de Noüy ring distraction technique to measure interfacial tension and the sessile contact angle of meconium-saline suspensions. Both were assessed in the absence and presence of perflubron. Meconium-saline suspensions inhibited surfactant activity. In contrast, the surface properties of perflubron were unaffected by the presence of meconium-saline suspensions. CONCLUSIONS These data are consistent with reported observations of increased lung compliance in perfluorocarbon-treated animals with meconium aspiration. In addition to these clinical implications, the novel interfacial tension technique described here could prove useful for assessing the interfacial properties of other poorly miscible biological fluids.