The in vitro and in vivo effects of several different inhibitors of carbohydrate metabolism have been studied. The in vitro addition of 5-methoxyindole-2-carboxylic acid (MICA), pent-4-enoic acid, and quinolinic acid to the perfusion medium significantly inhibited liver gluconeogenesis in 48-hour-starved rats (100% inhibition when MICA and quinolinic acid were added at 0.8 and 2.4 mM, respectively). In vivo the level of inhibition varied greatly depending upon whether MICA was administered by intragastric tube or intraperitoneal injection. In all cases the inhibitory capacity of MICA on liver gluconeogenesis was significantly higher when injected intraperitoneally. On the other hand, the administration of MICA produced a significant, dose-dependent, increase in renal gluconeogenesis in both fed and 48-hour-starved rats, more so when the inhibitor was administered by intraperitoneal injection.