Computer mouse use has become an integral part of office work in the past decade. Intensive mouse use has been associated with increased risk of upper extremity musculoskeletal disorders, including carpal tunnel syndrome. Sustained, elevated fluid pressure in the carpal tunnel may play a role in the pathophysiology of carpal tunnel syndrome. Carpal tunnel pressure was measured in 14 healthy individuals while they performed tasks using three different computer mice. Participants performed a multidirectional dragging ('drag and drop') task starting with the hand resting (static posture) on the mouse. With one mouse, an additional pointing ('point-and-click') task was performed. All mice were associated with similar wrist extension postures (p = 0.41) and carpal tunnel pressures (p = 0.48). Pressures were significantly greater during dragging and pointing tasks than when resting the hand (static posture) on the mouse (p = 0.003). The mean pressures during the dragging tasks were 28.8-33.1 mmHg, approximately 12 mmHg greater than the static postures. Pressures during the dragging task were higher than the pointing task (33.1 versus 28.0 mmHg), although the difference was borderline non-significant (p = 0.06). In many participants the carpal tunnel pressures measured during mouse use were greater than pressures known to alter nerve function and structure, indicating that jobs with long periods of intensive mouse use may be at an increased risk of median mononeuropathy. A recommendation is made to minimize wrist extension, minimize prolonged dragging tasks and frequently perform other tasks with the mousing hand.