Since astronaut time and energy are at a premium, effective countermeasures must be designed to maximize benefits while minimizing time/energy cost. Therefore, our intent was to design and evaluate a low volume, high intensity resistance training program (RTP) on the preservation of knee extensor and plantar flexor size, strength and neuromuscular function in response to unloading. A total of 32 subjects participated. Sixteen men underwent 21 days of unilateral lower limb suspension (ULLS) and were assigned to control (no RTP) (ULLS-CON, n=8) or countermeasures (ULLS-CM, n=8). The remaining subjects were ambulatory for 21 days and were assigned to no RTP (n=8) or countermeasures (n=8). Countermeasure subjects performed RTP every third day during the suspension period (total=6). The RTP consisted of 2 maximal isometric contractions (MVC), 1 set of 10 concentric/eccentric isotonic repetitions, and 1 set to exhaustion, at 80% of 1-repetition maximum (1RM). There was no change in muscle function in ambulatory subjects. Whole muscle cross sectional area (CSA) measured by computed tomography (CT) decreased 7% (thigh) and 7.5% (calf) in ULLS-CON (p<0.05), and was unchanged in ULLS-CM. MVC decreased 16.5% in both quadricep and calf muscles in ULLS-CON (p<0.05) and increased 6% in the quadricep of ULLSCM (p<0.05). Maximal concentric (CNC) and eccentric (ECC) isokinetic strength decreased an average of 18% and 17% in the knee extensors and plantar flexors of ULLS-CON, respectively (p<0.05) and was unchanged in ULLS-CM. 1RM decreased 16% in both quadricep and calf of ULLS-CON (p<0.05) and was unchanged in ULLSCM. Knee extensor work capacity, evaluated during 30 maximal CNC contractions (3.14 rad•sec-'), decreased 18% in ULLS-CON (p<0.05). Neural activation of knee extensors and plantar flexors was measured by electromyography (EMG). Submaximal v.lat, v.med, gast and sol EMG increased in ULLS-CON (p<0.05) and was unaltered in ULLSCM. Maximal EMG decreased 20% and 26% in v.1at and v.med, respectively in ULLSCON (p<0.05). ULLS-CM showed a 15% and 28% increase in v.med and gast maximal EMG (p<0.05). These data suggest knee extensor and plantar flexor muscle size, strength and neuromuscular function were preserved during unloading using a low volume, high intensity RTP performed every third day. / School of Physical Education