The notion that MHC class I-restricted CD8+ T (Tc) cells are capable of resolving autonomously infections with influenza virus is based largely on studies testing virus strains of low pathogenicity in CD4+ T (Th) cell-deficient/depleted mice. To test whether this holds also for pathogenic strains and to exclude possible contributions by B cells, we analyzed PR8 infection in Th cell-depleted B cell-deficient (μMT) mice. These mice, termed μMT (− CD4), showed 80% mortality after infection with a small dose of PR8, which resulted in insignificant mortality in intact or Th cell-depleted BALB/c mice. Infection of μMT (− CD4) mice with a virus of low pathogenicity was resolved without mortality, but, compared with intact BALB/c mice, with delay of∼ 5 and∼ 20 days from lung and nose, respectively. The low mortality of Th cell-depleted BALB/c mice suggested that B cells contributed to recovery in a Th-independent manner. This was verified by showing that transfer of 8–10 million T cell-depleted naive spleen cells into μMT (− CD4) mice 1 day before infection reduced mortality to 0%. The mechanism by which B cells improved recovery was investigated. We found no evidence that they operated by improving the lung-associated Tc response. Treatment of infected μMT (− CD4) mice with normal mouse serum spiked with hemagglutinin-specific IgM did not reduce mortality. Taken together, the data show that 1) the Tc response is capable of resolving autonomously (in conjunction with innate defenses) influenza virus infections, although with substantial delay compared with intact mice, and 2) B cells can contribute to recovery by a Th-independent mechanism.