Detailed experiments are presented which indicate that the properdin system is an inhibitor of Newcastle disease virus. Viral inhibition required all known components of the properdin system: properdin, all four components of complement and magnesium; the removal of any one constituent resulted in a loss of inhibition; the replacement of the constituent restored antiviral effect. The inhibition of virus was temperature-dependent. The process of inhibition by serum resulted in a decrease in the amount of properdin available in the serum without any measurable effect on the components of complement. The prolonged incubation of inactive serum-virus mixtures with cation-exchange resin resulted in the restoration of some, but not all, of the hemagglutinating activity of the virus. The requirements of the properdin system and the implication of these findings were discussed.