Using gene-targeted mice we have investigated whether perforin and/or interferon-gamma exert a direct regulatory effect on the expansion and contraction of antigen-specific CD8(+) T cells following infection with a virus (vesicular stomatitis virus) which is not controlled through these molecular effector systems. Unlike what has been observed when these molecules are essential for pathogen clearance, neither molecule was found to play an important role in regulating the kinetics of the virus-specific CD8(+) T cell response in the absence of antiviral effector activity.