Human peripheral blood leukocytes (PBL) from patients with chronic measles virus infection (SSPE [subacute sclerosing panencephalitis]) or from immune, adult humans (convalescent from acute childhood measles virus infection) are cytotoxic for target cells infected with measles virus as measured by a 51Cr assay. Specific release of 51Cr by immune PBL occurred with and without human antibodies added to measles virus-infected cultures. Maximal killing in the absence of added antibodies to measles virus was usually detected only after 15-18 h of incubation and with a high PBL to target ratio (100:1). When antibody to measles virus was added, PBL-mediated killing of virus-infected cells was not blocked. Killing was enhanced and maximal lysis occurred with fewer PBL and a shorter incubtion time. This cytotoxic reaction was inhibited in a dose-response manner upon the addition of Fab fragments of Ig[immunoglobulin]G containing antibodies to measles virus. On the average 4-5 .times. 105 antibody molecules bound per infected target cell before initiation of antibody-enhanced PBL killing. Depletion of glass-adhering or E[erythrocyte]-rosette-forming cells did not reduce PBL killing of measles virus-infected target cells in either system. Removal of non-E rosette or of EAC [E, antibody, complement] rosette-froming population of PBL almost completely abrogated cytotoxicity. When Fc-bearing cells were removed, killing of virus-infected target cells was concomitantly reduced. Lysis of measles virus-infected target cells did not require histocompatibility between the PBL and the target cell. Immunospecific lymphocyte killing was not enhanced by such a histocompatibility fit. The effector PBL involved in lysis of measles virus-infected targets are apparently not T [thymus-derived] cells but are probably K [antibody-dependent killer] cells. PBL obtained from patients with SSPE are apparently competent in killing measles virus-infected targets. Sera from SSPE patients did not contain a factor(s) that blocked PBL-mediated cytotoxicity.