The steady-state polarization (or anisotropy) of the fluorescent dye 1,6-diphenyl-1,3-5-hexatriene in amniotic fluid samples and the lecithin/sphingomyelin ratio of the samples were correlated with development of respiratory distress syndrome in newborns. We found that clinical samples have a variable endogenous fluorescence that reduces the observed polarization (or anisotropy). This background is a major interference in the assessment of fetal lung maturity by the polarization method. Correction for this interference, by also measuring the blank fluorescence and anisotropy of the sample, provides a clinical tool with a lower coefficient of variation than that of the more time-consuming lecithin/sphingomyelin ratio. The clinical correlation for 17 cases of respiratory distress syndrome in a high-risk population (60 births; twins counted as a single birth) indicates that the two methods are equivalent for predicting immature fetal lung status.