Uptake of carcinoembryonic antigen (CEA) by isolated rat alveolar cells was time, temperature, and concentration dependent (Kuptake = 2.4 x 10(-7) M). Pretreatment of the alveolar cells with colchicine inhibited internalization of CEA. Uptake of 125I-labeled CEA by alveolar cells required divalent cations and was inhibited by cold CEA and nonspecific cross-reacting antigen (NCA). The carbohydrate portion of CEA was modified by neuraminidase treatment and Smith degradation. The modified glycoproteins inhibited endocytosis by the alveolar macrophages, thus excluding nonreducing terminal carbohydrate residues as the recognition site of the receptor. Endocytosis of CEA was independent of native protein conformation since performic acid oxidized CEA and glycopeptides produced by pepsin digestion were inhibitory. Rat alveolar macrophages bound CEA with similar specificity to that of rat Kupffer cells. Alveolar macrophages, unlike Kupffer cells, did not rapidly exocytose the internalized CEA. Neither P388D1, a macrophage-like murine cell line, nor murine peritoneal exudate cells were capable of endocytosing CEA in vitro.