Animal experiments suggest developmental changes in surfactant homeostasis. The uptake and metabolism of [³H]dipalmitoylphosphatidylcholine-labeled liposomes with a surfactant-like composition were evaluated in type II cells isolated from rats of different postnatal ages. The early part of the uptake process (0-60 min) was more rapid and reached higher levels in cells from 2-day-old rats than in those from 7-day-old, 14-day-old, or adult rats. Temperature independence of this initial phase, differences in response to trypsin-EDTA or neuraminidase treatment, and the dependency of increased neonatal uptake on the presence of phosphatidylglycerol in liposomes suggested binding as a major mechanism of cell-lipid interaction. Although a two to three times larger amount of lipid was associated with neonatal cells, the metabolism of phosphatidylcholine, indicated by a decrease in label in phosphatidylcholine and an accompanying increase in sphingomyelin, was significantly smaller in 2-day-old than in adult cells. These studies support the hypothesis that neonatal and adult cells may have differences in the interaction with alveolar phospholipids and in the metabolism of phosphatidylcholine.