A safe and effective influenza vaccine is needed to prevent serious influenza illness in infants younger than 6 months of age. The purpose of this study was to determine whether two doses of the cold-adapted (ca) influenza A reassortant vaccine would be safe and immunogenic in this age group. In the first part of this study, infants received two doses of 10(5) or 10(6) 50% tissue culture-infectious dose (TCID50) of the ca influenza vaccine separately from routine immunizations. In the second part of this study two 10(6) TCID50 doses of the ca influenza vaccine were given with routine immunizations at 2 and 4 or 2 and 6 months of age. The ca influenza vaccine was well-tolerated by participants in both parts of this study. Two doses of the ca influenza vaccine were immunogenic in infants who received them separately from routine immunizations; 83% of vaccinees developed protective titers of serum hemagglutination-inhibition (HAI) antibody. In contrast, when the ca vaccine was administered with routine immunizations, protective HAI antibody titers were induced in only 20% of those immunized at 2 and 4 months of age and 50% of those immunized at 2 and 6 months of age. There were no statistically significant associations between HAI antibody response to ca influenza vaccination and dose schedule, presence of passively acquired maternal HAI antibody, ethnic group or breast-feeding status. Young age at the time of first immunization, however, appeared to correlate with decreased response to the hemagglutinin antigen of the influenza A virus.(ABSTRACT TRUNCATED AT 250 WORDS)