Mice have been shown to have increased susceptibility to bacterial and fungal superinfections between days 1 and 5 of acute murine cytomegalovirus (MCMV) infection. The current study demonstrated that, during the same period of the MCMV infection, migration of neutrophils into a subcutaneous sponge was impaired (1,300-2,000 cells/mm3 in MCMV-infected animals vs 6,000-7,000 cells in controls; P less than 0.01) and chemotaxis of neutrophils harvested from the sponge was decreased (chemotactic index of 1.5-2.1 in infected animals vs 5.4-5.7 in controls; P less than 0.01). The number of neutrophils in peripheral blood was not altered. Infectious MCMV was present in the neutrophil-rich fraction of peripheral white blood cells, suggesting that direct viral infection of neutrophils may contribute to altered function. These studies suggest that abnormalities in neutrophil function during acute cytomegalovirus infection may contribute to the enhanced susceptibility to bacterial and fungal infections that occurs in both experimental animals and humans.