The histopathology of the deep portion of the vastus intermedius (VIP) muscle from 13 rabbit hindlimbs immobilized in shortened position for 2-2.5 (n = 4), 3 (n = 3), 14 (n = 3) and 28 (n = 3) days and VIP muscles from 13 rabbit hindlimbs immobilized for the same time periods and subsequently remobilized for 4 weeks were compared. After 3 days of immobilization the VIP muscles displayed a 15% (p < 0.004) decline in muscle fibre diameter. By 2 weeks of immobilization fatty change was prominent and muscle fibre diameters had decreased to 56% (p < 0.0001) of control values. By 4 weeks of immobilization severe fibrotic damage of myofibres was observed and fibre diameters had decreased to 47% (p < 0.0001) of control values. Three days of immobilization followed by 4 weeks of remobilization led to marked fatty change as well as an increase in connective tissue in the affected VIP muscles. The muscle fibre diameter in these muscles was 71% (p < 0.0001) compared to the VIP immobilized for 3 days and 61% (p < 0.0001) compared to the control muscles. By 2-4 weeks of immobilization the subsequent remobilization did not aggravate the initial damage. We conclude that the morphology of VIP muscle immobilized for 3 days suffers more during a subsequent remobilization period than those immobilized for 14-28 days. These findings focus attention on the mechanisms operating at the onset of disuse muscle atrophy.