During lung injury, blood constituents may leak into the alveolar space and impair surfactant function. This study investigated possible interferences with the alveolar surfactant life cycle, by assessing the effects of various blood constituents on size, state of aggregation, and uptake of a natural, lipid-extracted bovine surfactant preparation (Alveofact) into isolated rat type II cells in primary culture. The results showed that plasma, serum, albumin, immunoglobulin G, bilirubin, and galactose inhibited uptake according to concentration. Fibrinogen and transferrin enhanced uptake; hemoglobin, fibronectin, and vitronectin had no effect. Uptake was also impaired when the blood constituents were washed off and the surfactant was added afterward. For some of the blood constituents, a direct interaction with the surfactant liposomes was observed, resulting in changes of liposome size and state of aggregation. However, no correlation between these changes and effects on uptake were found. During lung injury with increased permeability edema, a direct inhibition of surfactant lipid uptake by blood constituents might lead to a reduced delivery of surfactant components into type II cells and disturb surfactant metabolism.