Injection into mice of heat-killed Brucella abortus or aqueous ether-extracted B. abortus (Bru-pel) induced a "virus-type" interferon response, with peak titers at 6.5 h. The animals also were protected against challenge with otherwise lethal doses of Semliki forest virus. Extraction of either heated B. abortus or BRU-PEL with a mixture of chloroform-methanol (2:1, vol/vol) (C-M( yielded an insoluble residue (extracted cells) and a C-M extract. Neither extracted cells nor C-M extract alone induced interferon or afforded protection against Semliki forest virus infection in mice. Full interferon-inducing and protective activity was restored when extracted cells were recombined with C-M extract. C-M extract from heat-killed Escherichia coli also was effective in restoring activity to extracted Brucella cells. Neither heat-killed E. coli nor its C-M extract was active, nor was C-M estracted E. coli recombined with the C-M extract from B. abortus. These results suggest that the interferon-inducing and antiviral protective properties of B. abortus are constituted of a C-M-extractable component that is common to B. abortus and E. coli and an unextractable component that is unique to B. abortus.