The primary CD8(+) T-cell response protected most B-cell-deficient mu MT mice against intranasal infection with the HKx31 influenza A virus. Prior exposure did not prevent reinfection upon homologous challenge, and the recall CD8(+) T-cell response cleared the virus from the lung within 7 days. Depleting the CD8(+) T cells substantially reduced the capacity of these primed mice to deal with the infection, in spite of evidence for established CD4(+) T-cell memory. Thus, the control of this relatively mild influenza virus by both primary and secondary CD4(+) T-cell responses is relatively inefficient in the absence of B cells and CD8(+) T cells.