B acterial multiplication associated with virus infections is related to defects in in situ bactericidal (phagocytic) mechanisms of the lung. To determine whether the phagocytic defect was in bacterial ingestion and/or intracellular digestion, mice were infected with a sublethal dose of aerosolized Sendai virus and challenged 7 days later with a finely dispersed aerosol of Staphylococcus aureus. Groups of uninfected and virus-infected mice were sacrificed at 0, 6, 12, and 24 h after challenge, the lungs were perfused with formalin in situ, and the intra- or extracellular location of the bacteria was determined histologically. At 0 h, 49% and 51% of the staphylococci had an intracellular location in virus and nonvirus-infected lungs, respectively. With time, decreasing numbers of staphylococci were observed within the phagocytic cells of nonvirus-infected lungs, mostly as single organisms or in small clusters of less than four. In contrast, in focal area of virus-infected lungs, increasing numbers of phagocytic cells showed clumps of more than 25 bacteria/cell. These data demonstrate that virus-infected suppression of pulmonary antibacterial activity against S. aureus is related primarily to defects in intracellular processing mechanisms.