Trivalent cold-adapted recombinant (CR) influenza virus vaccines containing types A (H1N1 and H3N2) and B viruses were evaluated in two double-blind, placebo-controlled trials. Susceptible adults were randomly assigned to receive the following vaccines by intranasal drops 1 month apart: two doses of trivalent vaccine, bivalent CR influenza A (Bi A) vaccine followed by monovalent B (Mono B) vaccine or vice versa, or two doses of placebo. All vaccines were well tolerated. Shedding of each of the three vaccine viruses was reduced after the first dose of trivalent vaccine compared with primary vaccination with Bi A or Mono B. Shedding was also reduced after second vaccinations, whether homologous (trivalent-trivalent) or heterologous (Bi A/Mono B or Mono B/Bi A). Reduced viral shedding was associated with reduced serum antibody responses. Thus, both simultaneous and sequential inoculations of susceptible adults with CR influenza vaccine viruses result in reduced viral shedding and serum antibody responses.