Infection of L-cells with bluetongue virus results in inhibition of protein and deoxyribonucleic acid synthesis shortly after infection. No inhibition of ribonucleic acid synthesis is observed before 7 hours after infection. The length of the lag phase before the initiation of the inhibition of protein synthesis is dependent upon the number of infecting virus particles. An increase in the multiplicity of infection results in a decrease in the length of the lag phase. No new macromolecular synthesis is required for the induction of inhibition. Inhibition of viral replication by interferon or UV inactivation does not prevent the induction of inhibition. Virus neutralized by antiserum or inactivated by heat or acid treatment is unable to induce the changes in host cell metabolism.