Glycogen metabolism is a complex process which depends on the metabolic circumstances and the hormonal milieu. In this overview an intriguing new possibility has been emphasized--the possible central role of lactate in coordinating, with glucose, the net synthesis of glycogen. Since lactate changes acutely under many physiological circumstances, it would be a logical candidate for a signal which communicates to the liver the metabolic states of the periphery. It would then acutely determine the synthetic rate of glycogen synthesis within the range determined by the glucose concentrations which in turn could be said to reflect the nutritional state of the system. Interestingly, after oral glucose loading, portal glucose levels would be about 25% higher (Radziuk et al., 1978) relative to arterial. As seen from Figs 8 and 9 however the glycogen synthetic rate appears very sensitive to glucose (at a given lactate uptake). Everything else being assumed equal therefore, more glycogen would be synthesized than during intravenous loading with an equivalent peripheral concentration. This is indeed the case (Shulman and Rossetti, 1989). On the other hand, during equivalent loads, peripheral glucose levels are higher and the same quantity of glycogen is synthesized (Radziuk, 1989a, 1989b). If lactate is typical of other glucogenic substrates, then it is also logical that mixed meals with higher levels of portal substrate would maximize glycogen synthetic rates. Similarly, in diabetes where hyperglycemia and hyperlactatemia prevail, gluconeogenesis plays a predominant role in glycogen synthesis (Giaccari and Rossetti, 1992).(ABSTRACT TRUNCATED AT 250 WORDS)