Studies involving the biosynthesis and other aspects of the life cycle of the insulin receptor in human IM-9 lymphocytes as well in isolated rat adipose cells are under investigation. The receptors are labeled by either biosynthetic incorporation of radioactive sugars and amino acids or by techniques that label proteins or glycoproteins at the cell surface. After labeling the receptors are isolated by immunoprecipitation with anti-receptor antibodies and analyzed by NaDodSO4/polyacrylamide gel electrophoresis. In addition in order to characterize the subcellular sites responsible for the biosynthetic as well as for other processes of the life cycle of the receptor, three different subcellular fractions were prepared from rat adipose cells: 1) plasma membrane fraction; 2) high density microsomal fraction (enriched in endoplasmic reticulum; 3) low density microsomal fraction (enriched in Golgi apparatus. These results indicate that insulin receptor is synthesized in the endoplasmic reticulum as a Mr = 190,000 high mannose precursor. This precursor exhibits functional properties such as the ability to bind insulin and to undergo autophosphorylation in response to insulin. Processing of the presursor to yield the major subunits Mr = 135,000 and 95,000. In addition, some of the precursor appears to escape proteolytic cleavage but undergoes full processing of the carbohydrate chains and generates the Mr = 210,000 component which is inserted in the plasma membrane.