The present experiments were undertaken to assess hepatic lactate metabolism in the overnight-fasted, conscious dog after a physiological elevation in glucagon. Animals were given somatostatin plus intraportal insulin (243 microU . kg-1 . min-1) and glucagon (0.65 ng . kg-1 . min-1) to initially fix the pancreatic hormone levels at basal values. After a 40-min control period the glucagon level was increased to 527 +/- 27 pg/ml, while the insulin level was left unchanged (10 microU/ml). Fifteen minutes later blood lactate had increased by 215 +/- 24 mumol/l because of a marked increase in lactate output by the liver [2.4 +/- 2.0 to 10.0 +/- 3.8 mumol . kg . min (P less than 0.05)]. Subsequently, hepatic lactate output decreased, and after 3 h the liver was taking up lactate at a rate of 3.1 +/- 1.6 mumol . kg-1 . min-1 (P less than 0.05). Gut and renal lactate production were not significantly affected by glucagon. The rate of conversion of lactate and alanine to glucose had tripled after 3 h of hyperglucagonemia, while the efficiency with which the liver converted the incoming gluconeogenic precursors to glucose had doubled. The fractional extraction of alanine by the liver had more than doubled by 3 h, and net hepatic alanine uptake had increased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)