Insulin resistance has been recently distinguished as a syndrome associated with a clustering of metabolic disorders, including non-insulin dependent diabetes mellitus (NIDDM), obesity, hypertension, dyslipidemia and atherosclerosis. To date, it is thought that all of these disorders are the resulting consequences of primary insulin resistance. We propose that insulin resistance and the metabolic diseases mentioned can be caused by primary overactivity of the Na+/H+ exchange. This hypothesis has practical connotations for understanding the pathogenesis of the insulin resistance syndrome.