How does long-term training and the development of motor skills modify the activity of the primary motor cortex (M1)? To address this issue, we trained monkeys for ~1-6 years to perform visually guided and internally generated sequences of reaching movements. Then, we used [(14)C]2-deoxyglucose (2DG) uptake and single-neuron recording to measure metabolic and neuron activity in M1. After extended practice, we observed a profound reduction of metabolic activity in M1 for the performance of internally generated compared to visually guided tasks. In contrast, measures of neuron firing displayed little difference during the two tasks. These findings suggest that the development of skill through extended practice results in a reduction in the synaptic activity required to produce internally generated, but not visually guided, sequences of movements. Thus, practice leading to skilled performance results in more efficient generation of neuronal activity in M1.