A striking rash was produced in mice 4 days after intravenous injection of large doses of murine cytomegalovirus. Routine histology showed cell infiltration, vascular damage, and hemorrhage. Immunofluourescent staining showed dermal but not epidermal infection, and this appeared to be initiated after the localization in small blood vessels of circulating virus or of virus-containing leukocytes. The rash was accompanied by a high level of complement-requiring neutralizing antibodies in the serum and extensive deposition of immune complexes in the renal glomeruli containing immunoglobulin G, immunoglobulin M, and complement. When mice were depleted of complement by cobra venom factor, when antibody responses were reduced by cyclophosphamide treatment, or when a prostaglandin inhibitor (indomethacin) was given, the rash was much less severe. The role of direct viral damage and inflammatory and immune responses in the genesis of the lesions is discussed.