Insulin resistance is a well-known phenomenon in diabetic patients. Its occurrence in Type 1 (insulin-dependent) diabetes is thought to be due both to metabolic and immunological disturbances. In this context, a key role is attributed to the augmented release of the 'diabetogenic' hormones, adrenaline, glucagon, cortisol and growth hormone, as well as to hypertonic dehydration and to the presence of insulin-binding antibodies. In this connection it is noteworthy that among the 'diabetogenic' hormones adrenaline exerts the strongest insulin-antagonistic effect and that hypertonic dehydration is associated with impairment of insulin action and of non-insulin-dependent hepatic glucose uptake (in vitro), while hypotonic rehydration reduces the elevated hepatic glucose production in dehydrated Type 1 diabetic patients. By contrast, the generally only slightly elevated serum insulin-binding capacity in insulin-treated diabetics is probably of least importance in the development of insulin resistance, unless excessively high insulin antibody titres prevail.