The role of adaptive hormones and serum lipoproteins in the regulation of glucose-6-phosphate dehydrogenase (G-6-PDH) activity was investigated. The test was performed on experimental hepatic sections of Wistar rats. It was shown that timely regulation of G-6-PDH by epinephrine and hydrocortisone which inhibits the activity of enzyme is manifested through the cAMP-dependent mechanism. The cooperative effect of epinephrine, hydrocortisone and high-density lipoproteins that enables G-6-PDH activation was revealed. It was stated that only high-density lipoproteins of subpopulation III were capable of hormonal mediating. The effect was caused by the induction of enzyme synthesis and manifested through lysosome-dependent activation of chromatin.