Prior to vaccination with a trivalent influenza vaccine (AT/Texas, AB/Beijing, and BP/Panama), sera from 19 MS patients had a significantly higher mean level of antibody than 9 normal subjects to AT strain of influenza, but not to AB or BP strains. After Flu vaccination, the mean anti-AT and anti-AB antibody titers significantly increased 4-fold in 11 MS patients and 9 normal subjects. The ratio of MS responders (6/11), however, was lower than normal (8/9). The mean PBL proliferative response to the Flu antigens increased after vaccination significantly more in MS patients than in normal subjects, and increased in 9 of 11 MS patients and 3 of 9 normal subjects. Although MS patients responded to Flu antigens with higher antibody levels and proliferative responses of PBL, than normal subjects, a clinical protective effect of the vaccine against Flu was not clearly demonstrated in these patients, and vaccination did not cause or protect against exacerbation of MS.