Standard whole virus influenza vaccine (1974-1976) containing 700 chicken cell agglutinating (CCA) units of type A (Port Chalmers/1/75) or Port Chalmers plus Scotland/840/74) and 500 units of type B (HK/8/73) antigens was found to produce excessive systemic toxicity in adult volunteers. Using experimental monovalent A and B vaccines, most of the observed toxicity was shown to be associated with the B antigen. Injection of 500 CCA units or more of B vaccine was followed within 10-16 hours by malaise and chills in approximately one-third of vaccines. Chills, malaise, and local pain were more common in volunteers lacking prevaccination serum HI antibody than in those in whom this antibody was present. Toxicity was not related to the presence of endotoxin or bacterial contamination of vaccine; it appeared to be "intrinsic" to the viral antigen. The mechanism for the toxicity in man may be the same as the direct pyrogenic effect of influenza antigen for rabbits previously observed by others. Detoxification of the B antigen by prolonged exposure to formalin reduced the side effects of a 500 CCA unit dose to acceptable levels without impairing its antigenicity.