The administration of rabies-immune serum in addition to regular vaccination has been recommended as routine treatment in man after severe exposure to rabies virus. The inhibitory effect of passive antibody on active immunity induced against rabies by vaccination was investigated in rabbits. It was demonstrated that a dose of rabies-immune serum could completely block the neutralizing antibody response engendered by a very potent rabies vaccine. The inhibitory effect could be partially overcome if the number of vaccine doses was increased, if vaccination was started 15 days after serum administration, or if immune serum was given 12-24 hours after vaccination. Even under these circumstances, the antibody level was lower than that observed after administration of vaccine alone. Both 19S and 7S antibody exerted similar effects.