In previous experiments we have shown that the rapid clearance in rats of alcohol dehydrogenase, lactate dehydrogenase M4, and the mitochondrial and cytosolic isoenzymes of malate dehydrogenase is largely due to endocytosis by macrophages in liver, spleen and bone marrow. Competition experiments indicated that the dehydrogenases as well as adenylate kinase and creatine kinase MM are endocytosed via the same receptor. We suggested that this receptor contains a group with affinity for the nucleotide-binding sites of the enzymes. We now demonstrate that competition also occurs between mitochondrial malate dehydrogenase and mitochondrial aspartate aminotransferase, which does not require a nucleotide for its activity. At low doses, mitochondrial aspartate aminotransferase was cleared following first-order kinetics (half-life: 19 min). Simultaneous injection of a high dose of mitochondrial malate dehydrogenase strongly retarded the clearance of the aminotransferase. These results make unlikely the hypothesis that a nucleotide-binding site is involved in recognition of enzymes by macrophages.