In response to added catecholamines, isolated trout (Salmo gairdneri) hepatocytes substantially increase the output of glucose into the surrounding medium. This effect is due to activation of glycogen breakdown concomitant with increases in gluconeogenesis and cell respiration. Each metabolic parameter is activated to a similar extent. In hormone-treated and untreated cells, glycogenolysis accounts for more than 97% of glucose production. Activation of glycogen phosphorylase is implicated in the degradation of cell glycogen, while increased flux through the gluconeogenic pathway from lactate is associated with inactivation of pyruvate kinase, possibly through enzyme phosphorylation as indicated by the activity ratio measured at low and saturating concentrations of phosphoenolpyruvate. From studies with specific adrenergic agonists and antagonists, we conclude that stimulation of glycogenolysis and gluconeogenesis in trout hepatocytes is consistent with a beta-adrenergic effect. Results are inconclusive with respect to catecholamine-mediated activation of cell respiration. None of the monitored cell acid-base variables (pH, PCO2, [HCO3-]) are implicated in the catecholamine-dependent changes in metabolic output of hepatocytes. Imposed hypercapnic conditions (increased medium PCO2 and decreased medium pH), which cause changes in cell acid-base parameters, result in a depression of lactate oxidation and gluconeogenesis, while the rate of glycogenolysis is not affected. In addition, the total amounts of glycogen phosphorylase and pyruvate kinase assayable are negatively affected by hypercapnic treatment of hepatocytes. Under hypercapnic conditions, cells are highly responsive to adrenergic agonists. It appears that--especially in the long term--the catecholamine-dependent activation of gluconeogenesis may compensate for the acid-base-dependent shortfall in glucose output by the liver.