Activity markers cytochrome oxidase (CO) and glutamic acid decarboxylase (GAD) were analyzed in the primary somatosensory cortex of raccoons that underwent digit amputation. Subjects recovered for 2, 15, and 23 weeks following amputation of the fourth forepaw digit. Histochemistry was used to assess relative activity levels of both enzymes. We found a pronounced decrease in the numbers of CO intense patches in the cortical gyrus that had lost its original sensory input from the fourth digit. This decrease in CO activity was still apparent 15 weeks post-amputation. Conversely, no clear decrease in GAD levels could be identified in connection with the amputation procedure. Our findings present evidence that a significant decrease in metabolic activity results from the loss of the primary afferent sensory drive. The remaining GAD activity suggests that the absence of electrical activity, characteristic of reorganizing cortex, is likely to depend in part on lateral inhibitory cortical connections.