Minimal numbers of CD8+ T cells are found in bronchoalveolar lavage (BAL) populations recovered from Sendai virus-infected mice that are homozygous (-/-) for a beta 2-microglobulin (beta 2-m) gene disruption. The prevalence of the CD8+ set was substantially increased in the pneumonic lungs of 8-12-week radiation chimeras made using substantially class I major histocompatibility complex (MHC) glycoprotein-negative beta 2-m (-/-) recipients and normal beta 2-m (+/+) bone marrow. Even so, the CD8+ (but not the CD4+) lymphocyte counts were still much lower than in the (+/+)-->(+/+) controls. The (+/+)-->(+/+) and (+/+)-->(-/-) chimeras cleared Sendai virus and potent virus-immune CD8+ cytotoxic T lymphocytes (CTL) specific for H-2Kb+viral nucleoprotein peptide were found in the BAL from both groups. However, following in vivo depletion of the CD4+ population, only the (+/+)-->(+/+) mice were able to deal with the infection. Similarly, adoptively transferred, H-2Kb-restricted CD8+ T cells from previously-primed (+/+) mice also failed to clear virus from the lungs of (+/+)-->(-/-) chimeras infected within 2 weeks of reconstitution with bone marrow, though they were effective in the (+/+)-->(+/+) controls. Sendai virus-immune CD8+ T cells are thus unable to eliminate virus-infected beta 2-m (-/-) lung epithelial cells that might be thought to be expressing very small amounts of either isolated class I heavy chain, or class I MHC glycoprotein that has bound beta 2-m derived from beta 2-m (+/+) T cells or macrophages present in the pneumonic lung. Furthermore, the CD8+ CTL that are being exposed to beta 2-m (+/+) stimulators in the BAL population cannot operate in some bystander mode to clear virus from respiratory epithelium.