Objective: This study compares the distribution of exogenous pulmonary surfactant in piglets with and without meconium instillation. Eight 2-4 kg Yorkshire-type piglets were intubated and supported with positive pressure ventilation (PPV) and oxygen to maintain inspiratory tidal volumes of approximately 10 ml/kg and oxygen saturations of > 95%. Each piglet was randomized to receive either meconium followed one hour later by surfactant(MS) or surfactant only (SO). In the MS group 5 ml/kg of a 30% solution of human meconium was delivered via a feeding tube in two divided doses with the piglet in the right then left lateral position. 4 ml/kg 3H-DPPC radiolabeled surfactant was delivered in the same manner to all animals. The pigs were euthanized 4 hours after surfactant instillation in both groups. The lungs were dissected, frozen, and later sectioned into pieces with a mass of 0.71 ± 0.14 g (mean ± 1 SD). The location and mass of each piece were recorded. Tritium counts were determined by liquid scintillation and the density of surfactant for each piece was calculated by count/mass ratio. Data were standardized as multiples of the mean (MoM) and plotted as histograms. The variances were compared by the F-test. ANOVA compared density of surfactant by lobes. Results: The histograms indicate heterogeneous distribution of surfactant in both groups, with more heterogeneity of distribution in the MS group (p<0.002). When mean surfactant density by lobe is considered, there are no significant differences between the two groups. Conclusions: Tracheal instillation of meconium in this model significantly increased the heterogeneity of surfactant distribution. Meconium aspiration results in heterogeneous lung mechanics and surfactant therapy may exacerbate this heterogeneity. This study was funded in part by Ross Products Division, Abbott Laboratories.