This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure (COP) motion associated with arm movement of eight subjects who experienced long-duration spaceflight (3-6 mo) aboard the Mir space station. Surface electromyography, arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions before and after spaceflight. Subjects generally displayed compromised postural control after flight, as evidenced by modified COP peak-to-peak anterior-posterior and mediolateral excursion, and pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e., when subjects were attempting to maintain upright posture in response to self-generated perturbations). These findings suggest that, although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long-duration spaceflight.