Mice sensitized to individual respiratory syncytial (RS) virus proteins show distinct patterns of immunity and pulmonary pathology when challenged with live virus. To explore the immune mechanisms responsible for the differences in postvaccination disease, BALB/c (H-2d) mice were primed by scarification with recombinant vaccinia viruses (rVV) expressing the major glycoprotein (G), fusion protein (F), phosphoprotein (P), nucleoprotein (N), or second matrix (22K) protein of RS virus. Ag-stimulated spleen cell cultures gave rise to CD3+TCR-alpha beta + T cell lines. Those from rVV-F-primed mice contained a mixture of CD8+ and CD4+ T cells, whereas those specific to G, N, and P were mostly CD4+. In contrast, 22K-specific lines were mostly CD8+. F- and 22K-specific lines showed virus-specific CTL activity against H-2d targets, but the lines from rVV-G-, -N-, and -P-primed mice did not. The F-specific lines contained Th cells that released an excess of IL-2 and some IL-3 but little IL-4 or IL-5 (i.e., a "Th1" pattern). In contrast, the G-specific line released IL-3, IL-4, and IL-5 but little IL-2 (i.e., a "Th2" pattern). The 22K line contained IL-3-releasing T cells. Staining of T cell subsets for CD45RB varied in intensity in different lines, consistent with the cytokine secretion profiles of the Th cells that they contained. Because different RS virus proteins (given in the same form by the same route) prime for functionally different T cells, the ways in which individual proteins are processed and presented might be important in determining these patterns of immunity.