The high-molecular-mass aminoacyl-tRNA synthetase complexes in higher eukaryotes are discrete non-artifactual multienzyme complexes of similar composition which can be purified from different tissues of different species by different techniques. These high-Mr complexes are composed of synthetases in simple stoichiometric ratios. The synthetases most often found in high-Mr complex are those specific for Arg, Gln, Glu, Ile, Leu, Lys, and Met. Several synthetases are shown to contain carbohydrates suggesting a major difference between the eukaryotic and prokaryotic enzymes and the possibility that carbohydrates may be involved in complex formation. The functional significance of the high-Mr complexes is unclear but reduction of thermolability of the synthetases by complex formation appears well established. The activation and inactivation of synthetase activities in high-Mr complex by dephosphorylation and phosphorylation and the ability of the synthetases to synthesize Ap4A suggest that synthetases in complexes may be intricately involved in control of DNA replication, transcription, and translation. Localization of Met-tRNA synthetase to the endoplasmic reticulum by immunfluorescence microscopy suggests that part of the protein synthesis machinery is highly organized on intracellular membranes and that this may provide for compartmentation of intracellular amino acid and aminoacyl-tRNA pools.