Pandemic H1N1 influenza vaccine antigens are currently being manufactured. The MF59 adjuvant has an established safety profile in humans and a proven ability to increase responses to some influenza vaccines in humans. To inform initial decisions on the use of these vaccine components to protect human populations, we have immunized mice with MF59-adjuvanted or non-adjuvanted pandemic influenza vaccine. Immunizing unprimed mice with a single dose of MF59-adjuvanted vaccine elicits functional antibody titers equivalent to those associated with protection of humans from seasonal influenza. Without adjuvant, two doses are required for a robust antibody response. Unadjuvanted vaccines with 0.5 and 1 microgram of antigen elicit equivalent titers. These data support including MF59 in pandemic flu vaccines to rapidly protect young adults and children, who may have little or no previous exposure to influenza infection or immunization.