Patients with subacute sclerosing panencephalitis (SSPE) are presumed to lack specific cellular immunity against measles virus. In order to test this hypothesis in vitro, the interaction between peripheral lymphocytes and measles virus-infected tissue culture cells was investigated in 10 SSPE patients. Human fibroblasts, either uninfected or carrying a persistent measles virus infection, were labeled with 51Cr and incubated with lymphocytes for 18 to 20 hr in the absence of antibody and complement. Peripheral lymphocytes from measles sero-positive and sero-negative individuals were tested, and the system was found to be virus specific. The lymphocytes from the 10 SSPE patients caused specific cytotoxicity of target cells. A correlation was not found between antibody titer and specific 51Cr release. It could also be demonstrated that target cell destruction was not mediated by monocytes or B lymphocytes. These in vitro studies suggest that SSPE patients do not have a specific defect of cellular immunity against measles virus.