Changes in proprioception (movement and position perception), facilitated by alterations in muscle spindle afferent activity, arise following repetitive muscle activity, especially if fatigue ensues. Consequently, a hypothesis was put forth that work-related musculoskeletal disorders (both in the genesis and spread of muscle pain) might be attributed to diminished proprioceptive function. PURPOSE: To determine the effect of computer mouse use on proprioception. METHODS: Position sense acuity of the wrist joint for 23 normal volunteers (11 females and 12 males) was determined before and after a laboratory model of repetitive mouse use entailing painting small squares on the computer screen uninterrupted for 45 minutes. Wrist position sense was determined by noting the angular error for subjects actively reproducing a series of 15 test trials randomly displaced between 0○ and 30○ of flexion, while starting at 30○ of extension. The variability of error (VE) (i.e. standard deviation of the 15 trials) was computed as the assessment variable of accuracy. In addition, subjective fatigue was assessed using the Borg scale before, after and for each 5 min-interval during the painting protocol. RESULTS: A 2-way ANOVA revealed an increase in VE following mouse use for the group (p < 0.05), but no difference between gender was detected. Fatigue ratings increased throughout the painting protocol for the group (p < 0.001); furthermore a significant interaction was found between gender (p < 0.05), which displayed as males exhibiting a steep increase in the first 10 minutes followed by a plateau, while for females a constant linear increase was observed throughout. CONCLUSIONS: Since optimal motor control is largely dependent on proprioception, it may be implied that extended mouse use could lead to increased workload, thereby increasing intramuscular metabolites and/or inflammatory substances which would further impact proprioception (i.e. an unfavorable cycle of events). Thus, the current findings may provide insight into the poorly understood mechanism behind computer related musculoskeletal disorders. Supported in part by the Swedish Council for Work Life Research, and technically by Monica Edstrom and Majken Rahm.