Employing a 51Cr release cytotoxicity microassay, and using both measles-and SSPE-infected target cells, four patients with documented SSPE were evaluated for specific cellular and humoral immunity. Mononuclear leukocytes from SSPE patients and control subjects exhibited comparable cytotoxicity. Serum and CSF from these SSPE patients inhibited the cellular response to SSPE-infected cells but not to measles-infected cells. Moreover, fresh whole serum alone from control donors produced significant 51Cr release from both cell lines, whereas SSPE whole serum was effective only against measles-infected cells. CSF from an additional ten patients with SSPE was examined for inhibitory activity: seven of these completely blocked and one partially blocked cell-mediated cytotoxicity to SSPE-infected cells. Preliminary characterization of the serum inhibitory factor suggested that it is IgM or antigen-antibody complexes. These data also suggest antigenic differences between the SSPE and measles viruses.