The aim of the present study was to investigate the changes in thickness, fascicle length (L (f)) and pennation angle (theta) of the antigravity gastrocnemius medialis (GM) and vastus lateralis (VL) muscles, and the non-antigravity tibialis anterior (TA) and biceps brachii (BB) muscles measured by ultrasonography in ten healthy males (aged 22.3 +/- 2.2 years) in response to 5 weeks of horizontal bed rest (BR). After BR, muscle thickness decreased by 12.2 +/- 8.8% (P < 0.05) and 8.0 +/- 9.1% (P < 0.005) in the GM and VL, respectively. No changes were observed in the TA and BB muscles. L (f) and theta decreased by 4.8 +/- 5.0% (P < 0.05) and 14.3 +/- 6.8% (P < 0.005) in the GM and by 5.9 +/- 5.3% (P < 0.05) and 13.5 +/- 16.2% (P < 0.005) in the VL, again without any changes in the TA and BB muscles. The finding that amongst the antigravity muscles of the lower limbs, the GM deteriorated to a greater extent than the VL is possibly related to the differences in relative load that this muscle normally experiences during daily loading. The dissimilar response in antigravity and non-antigravity muscles to unloading likely reflects differences in loading under normal conditions. The significant structural alterations of the GM and VL muscles highlight the rapid remodelling of muscle architecture occurring with disuse.