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1. To test further the hypothesis that brain protein synthesis is necessary for fever, three structurally similar trichothecene antibiotics were injected into the cerebral ventricles of rabbits. They were 3,15-diacetoxy-12-hydroxytrichothec-9-ene (DAHT), 3,15-didesacetyl-calonectrin (DDAC) and T-2 toxin. Their actions on hypothalamic incorporation of [14C]leucine and fever were compared. 2. DDAC (60 micrograms) and T-2 toxin (10 micrograms) strongly inhibited leucine incorporation and fever. DAHT (60 micrograms) did not diminish fever and had a smaller effect upon leucine incorporation. 3. The findings strengthen considerably earlier suggestions that brain protein synthesis is an essential step in pyrogenesis.