Objective: To test whether unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle injury. Design: Before-after trial. Setting: General community. Patients or Other Participants: Two women and 5 men (73+/-3kg [mean+/-SE]) who were active college students but were not trained in lower body resistance exercise volunteered. Intervention: Five weeks of unilateral lower limb suspension (ULLS), which has been shown to decrease strength and size of the unloaded, left, but not load-bearing, right quadriceps femoris muscle group (QF) by 20% and 14%, respectively; performance of 10 sets of ten eccentric actions with each QF immediately after the ULLS strength tests with a load equivalent to 65% of the post-ULLS eccentric 1-repetition maximum. Main Outcome Measure(s): Concentric and eccentric 1-repetition maximum for the left, unloaded and the right, load-bearing QF measured immediately after ULLS and 1, 4, 7, 9, and 11 days later; cross-sectional area and spin-spin relaxation time (T2) of each QF as determined by magnetic resonance imaging and measured the last day of ULLS and 3 days later. Results: The mean load used for eccentric exercise was 23+/-2 and 30+/-3kg for the left, unloaded and right, load-bearing QF, respectively. The concentric and eccentric 1-repetition maximum for the unloaded and already weakened left QF was further decreased by 18% (p =.000) and 27% (p =.000), respectively, 1 day after eccentric exercise. Strength did not return to post-ULLS levels until 7 days of recovery. The right, load-bearing QF showed a 4% decrease (p =.002) in the eccentric 1-repetition maximum 1 day after eccentric exercise, The left, unloaded QF showed an increase in T2 (p =.002) in 18% of its cross-sectional area 3 days after the eccentric exercise, thus indicating muscle injury. The right, load-bearing QF showed no elevation in T2 (p =.280). Conclusion: Unloading increases vulnerability to eccentric exercise-induced dysfunction and muscle injury, even at relatively light loads. (C) 1996 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine ann Rehabilitation.