We tested the hypothesis that contracting skeletal muscle can rapidly restore force development during reperfusion after brief total ischemia and that this rapid recovery depends on O₂ availability and not an alternate factor related to blood flow. Isolated canine gastrocnemius muscle (n = 5) was stimulated to contract tetanically (isometric contraction elicited by 8 V, 0.2-ms duration, 200-ms trains, at 50-Hz stimulation) every 2 s until steady-state conditions of muscle blood flow (controlled by pump perfusion) and developed force were attained (3 min). While maintaining the same stimulation pattern, muscle blood flow was then reduced to zero (complete ischemia) for 2 min. Normal blood flow was then restored to the contracting muscle; however, two distinct conditions of oxygenation (at the same blood flow) were sequentially imposed: deoxygenated blood (30 s), blood with normal arterial O₂ content (30 s), a return to deoxygenated blood (30 s), and finally a return to normal arterial O₂ content (90 s). During the ischemic period, force development fell to 39 ± 6 (SE)% of normal (from 460 ± 40 to 170 ± 20 N/100 g). When muscle blood flow was restored to normal by perfusion with deoxygenated blood, developed force continued to decline to 140 ± 20 N/100 g. Muscle force rapidly recovered to 310 ± 30 N/100 g (P < 0.05) during the 30 s in which the contracting muscle was perfused with oxygenated blood and then fell again to 180 ± 30 N/100 g when perfused with blood with low PO₂. These findings demonstrate that contracting skeletal muscle has the capacity for rapid recovery of force development during reperfusion after a short period of complete ischemia and that this recovery depends on O₂ availability and not an alternate factor related to blood flow restoration.