Infection of rhesus monkeys with measles virus induced specific complement-dependent cytolytic antibodies during the early phase of acute infection. The development of maximal levels of the complement-dependent cytolytic antibodies appears to be dependent on the respiratory rather than the parenteral route of infection and on the use of live rather than killed measles virus. These levels of cytolytic antibodies seem to be independent of levels of simultaneously developing neutralizing and hemagglutinating antibodies. It is proposed that complement-dependent cytolytic antibodies play an important role in the elimination of acute measles virus in vivo by lysing the foci of infected cells and by blocking the spread of virus by cell fusion.