Monkeys were trained in a serial reaction time task to produce hand movements according to changing locations of visual targets. In most trials, targets followed the same sequence repeatedly, whereas in other trials targets were presented in random locations or switched unpredictably between two alternative sequences. Single-unit activity was recorded from the caudal supplementary motor area (SMA-proper). Based on the activity associated with random movement sequences, effects of hand position and movement direction were evaluated. Activity was influenced by the hand position in ~60% of the neurons, and the movement direction influenced the activity of 51% of the neurons. In addition, 37 and 71% of SMA neurons displayed nonstationarity in their activity across successive movements within a given trial and across trials, respectively. Such nonstationarity in the ongoing neural activity and the effects of performance-related variables were evaluated using a regression model and separated from learning-related activity changes. About a third of SMA neurons displayed gradual changes in neural activity related to experience with a movement sequence across trials. Furthermore, about a quarter of SMA neurons showed similar changes within individual trials. When the individual movements included in the frequently repeated movement sequences were introduced unexpectedly, learning-related changes in neural activity were reduced, indicating that many SMA neurons changed their activity in relation to the learning of particular movement sequences. These results suggest that the pattern of neural activity in the cortical network involved in the control of movement sequences can be modified continuously by experience.