After injury, axons of the adult mammalian brain and spinal cord exhibit little regeneration. It has been suggested that axon growth inhibitors, such as myelin-derived Nogo, prevent CNS axon repair. To investigate this hypothesis, we analyzed mice with a nogo mutation that eliminates Nogo-A/B expression. These mice are viable and exhibit normal locomotion. Corticospinal tract tracing reveals no abnormality in uninjured nogo-A/B^−/− mice. After spinal cord injury, corticospinal axons of young adult nogo-A/B^−/− mice sprout extensively rostral to a transection. Numerous fibers regenerate into distal cord segments of nogo-A/B^−/− mice. Recovery of locomotor function is improved in these mice. Thus, Nogo-A plays a role in restricting axonal sprouting in the young adult CNS after injury.