We have evaluated the use of live cold-adapted influenza A and B virus vaccines in the elderly. Cold-adapted influenza A and B virus vaccines are safe and modestly immunogenic in individuals over 65 years of age. However, our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest. Administration of combined cold-adapted influenza A and inactivated influenza vaccine has resulted in slightly higher frequencies of local and systemic humoral immune responses than inactivated vaccine alone in some, but not all, studies. In a double-blind field trial conducted in nursing homes over a 3 year period, combined cold-adapted influenza A (H3N2) and trivalent inactivated influenza vaccine resulted in a 60% decrease (95% CI, 18-82%) in the rate of laboratory documented influenza A compared with inactivated vaccine alone. Further studies of multivalent cold-adapted influenza vaccines used in combination with inactivated vaccine should be performed.