To establish the existence of predominant right leg involvement in Coxsackievirus B1-induced myositis (CB1 myositis) 189 neonatal CD1 Swiss mice were inoculated with 300 pfu CB1, and regularly observed for posture, mobility, and gait. After 2 and 4 weeks, quantitative comparison of motor dysfunction of right and left leg yielded an asymmetry score; on light microscopy mononuclear cell infiltration and muscle fiber necrosis were quantified in bilateral hamstring muscles, using a five-grade scale (0-4). Motor asymmetries were seen during acute viral myositis as soon as hind leg dysfunction appeared, and animals with a predominant dysfunction of one leg preserved that preference throughout the observation period. At 2 weeks, mice with predominant right leg dysfunction (n = 34) significantly outnumbered those with predominant left leg dysfunction (n = 11) (p = 0.01). At 2 and 4 weeks, infiltration and necrosis in hamstrings from legs with predominant dysfunction were not higher than in those from contralateral legs, and infiltration in right-sided hamstrings was not higher than in left-sided ones, nor was infiltration at 4 weeks. At 4 weeks right-sided muscles were more necrotic (mean +/- SD, 1.8 +/- 1.5) than left-sided muscles (1.1 +/- 1.2; p = 0.03). In the absence of predominant inflammatory disease of the right leg, we interpret the hind leg asymmetry as a preferential use of the left leg, due to left-leggedness, and suggest that in CD1 Swiss mice left-leggedness is associated with increased susceptibility to CB1 myositis.