A RECENT investigation from this laboratory1 demonstrated that psychotic depression is associated with low rates of glucose utilization (k) and high levels of serum insulin following glucose injection. Patients with neurotic depression did not demonstrate these abnormalities. This abnormality, a resistance to endogenous insulin, returned toward normal when the patient improved. These findings, which could not be accounted for by initial levels of serum human growth hormone (HGH), age, or nutritional state, suggested that psychotic depression is associated with a type of endogenous insulin resistance unlike that of any previously described condition. Recent studies by Steiner et al2 and Shaw and Chance3 have shown that the routine serum insulin radioimmunoassay measures both insulin and the insulin precursor, proinsulin, but that proinsulin is not biologically active until enzymatically degraded to insulin. It is, therefore, possible that the higher serum