This study examined the effect of short-term unweighting on strength and size of lower limb muscle groups to predict probable responses to planned 16-d Shuttle flights. Subjects were 10 healthy males, exposed to 16 d of lower limb suspension (LLS). All ambulatory activity was performed on crutches while wearing a shoe with a 10-cm thick sole on the right foot. This eliminated ground contact by the left foot, and thereby, body weight bearing by the left lower limb. Biopsies of the left vastus lateralis muscle and T1 weighted magnetic resonance (MR) images (1.5 Tesla, TR/TE 600/20, 4 nex, 48 cm rectangular FOV, 10 mm transaxial slices at 5-mm intervals) of both thighs were used to examine muscle morphology. The in vivo speed-torque relation for the left and right quadriceps femoris (QF) muscle group was used to measure strength. Fiber type composition and average cross-sectional area were not altered by LLS. The speed-torque relation for the left QF was down-shifted 12% (p < 0.05) after LLS. There was no effect of speed or type of muscle action (eccentric, isometric, or concentric). The speed-torque relation for the right QF showed no change after LLS. Average cross-sectional area of the left QF in eight MR images of the mid-thigh decreased (p < 0.05) 8% with LLS (70 +/- 3 to 64 +/- 4 cm2), while the right QF showed no change (72 +/- 4 to 72 +/- 4 cm2). The hamstring muscle group showed no change in average cross-sectional area after LLS.(ABSTRACT TRUNCATED AT 250 WORDS)