Skilled use of tools requires us to learn an "input-output map" for the device, i.e., how our movements relate to the actions of the device. We used the paradigm of visuo-motor rotation to examine two questions about the plasticity of input-output maps: 1) does extensive practice on one mapping make it difficult to modify and/or to form a new input-output map and 2) once a map has been modified or a new map has been formed, does this map survive a gap in performance? Humans and monkeys made wrist movements to control the position of a cursor on a computer monitor. Humans practiced the task for approximately 1.5 h; monkeys practiced for 3-9 yr. After this practice, we gradually altered the direction of cursor movement relative to wrist movement while subjects moved either to a single target or to four targets. Subjects were unaware of the change in cursor-movement relationship. Despite their prior practice on the task, the humans and the monkeys quickly adjusted their motor output to compensate for the visuo-motor rotation. Monkeys retained the modified input-output map during a 2-wk gap in motor performance. Humans retained the altered map during a gap of >1 yr. Our results show that sensorimotor performance remains flexible despite considerable practice on a specific task, and even relatively short-term exposure to a new input-output mapping leads to a long-lasting change in motor performance.