Because smallpox vaccination was recently shown to induce a strong vaccinia virus-specific CD8(+) CTL- and IFN-γ–producing T cells detectable by more cumbersome research laboratory methods (cytotoxic, proliferative, or ELISPOT assays) (8,9), we evaluated the feasibility of an easy, rapid, and sensitive assay to monitor T-cell responses after recent vaccination against smallpox; the assay can potentially be used as a routine diagnostic assay. This evidence concerns the gene IFNG and smallpox.