The metabolism of alanine and several other gluconegoneic substrates was studied in anesthtized fed and fasted rats, i.e., rats with low and high rates of gluconeogenesis. Glutamine was released by the hindquarter (muscle) in both groups, whereas lactate, pyruvate, and alanine were taken up in fed rats and were released during starvation. Despite this, blood levels of alanine, lactate, and pyruvate were diminished in fasting rats, suggesting increased extraction by liver. Treatment of fasted rats for 24 h with phloridzin caused glycosuria and secondarily led to hypoglycemia and an intensification of the chargesobserved with fasting, i.e., hyperketonemia, hyperglucagonemia, and increased gluconeogenesis (assessed by urea N excretion). Blood alanine was decreased, even though the release of alanine from muscle was increased. Pretreatment with triamcinolone and administration of exogenous alanine both attenuated the hypoglycemia and ketosis, It is concluded that 1) in states of heightened gluconeogenesis, alanine release from muscle may not keep pace with extraction by liver and blood alanine decreases; 2) the release of alanine, lactate, and pyruvate from muscle parallel each other suggesting common control factors; and 3) in the red state muscle is an important site of lactate disposition.