Spontaneous running in activity wheels was measured in more than 4,000 mice belonging to 13 inbred strains and 31 F1 hybrid groups. A significant proportion of the hybrids displayed behavioral hybrid vigor or heterosis, i.e., in wheels they out-distanced both inbred parents. Mice produced by crossing distantly related inbred strains showed less hybrid vigor than F1 hybrids resulting from the crossing of unrelated inbred strains. These results were found to be consistent with current genetic theories of heterosis.