The oral glucose tolerance test and immune reactive insulin level determination were performed on 100 non-obese healthy elderly and 40 young and middle-aged non-obese healthy subjects. In about 60% of the elderly an altered glucose tolerance test was found, but the insulin level was increased in the whole group of elderly subjects. This means an insulin-resistant state with aging. Further investigations were carried out to determine some possible causes of this insulin resistance. The chromium level in sera and granulocytes of elderly was significantly decreased as well as the insulin receptor numbers and the affinity to erythrocytes. In contrast, when the cyclic nucleotide levels were investigated in granulocytes under in vitro stimulation, an age-dependent increase of cAMP level was found and an unresponsiveness of cGMP, which ranged between mild and severe degrees. Concomitantly, all these changes found could contribute to the insulin resistance at the receptor and post-receptor levels with aging.