Meconium aspiration syndrome is a disease of the newborn characterized by pneumonitis and surfactant inhibition. We have previously demonstrated that isolated adult rat type II pneumocytes (T-2) in culture increased phosphatidylcholine secretion but decreased the secretion of extracellular matrix proteins without cellular toxicity as evaluated by vital dye exclusion in the presence of meconium. The interaction in vivo of T-2 cells with the basement membrane and adjacent cells may be important in the pathophysiology of meconium aspiration syndrome, however this cannot occur with isolated T-2 cells. To maintain the relationship of T-2 cells to the basement membrane and adjacent parenchymal cells, we developed a new model using fetal lung explants, examining the effect of meconium on fetal lung phospholipid and surfactant protein synthesis. Sixteen rat fetuses were removed from a healthy female rat at 21 days gestation. Under a dissecting microscope the trachea of each fetus was identified and cannulated. The lungs were injected intratracheally with 100ml of either 1% human meconium (1%=3mg dry wt./ml), or Waymouth media (control). The lungs were removed, cut on a tissue chopper into 1mm cubes, then incubated at 37° in 95% oxygen. Lung explants were sampled and the media changed at 24, 48, and 72 hours. Each sample was homogenized then solubilized in a 0.1% Triton solution. Immunoblot assays for surfactant proteins A and B (SP-A, SP-B) were performed and standardized to total protein. When compared to control explants, SP-B in meconium explants tended to decrease, while SP-A increased at each of the three days. Phospholipids in meconium explants were no different from controls. The data indicates that meconium may have a significant effect on fetal explant T-2 cell function. We suggest that this model more closely relates to T-2 cell function in vivo.