This study evaluated the safety, immunogenicity, and protective efficacy of vaccines containing purified recombinant uncleaved hemagglutinin (rHA0) from influenza A/Beijing/32/92 (H3N2) virus. In a randomized, double-blinded trial, 127 adult volunteers were immunized with 15 micrograms of rHA0, 15 micrograms of rHA0 plus alum, 90 micrograms of rHA0, licensed subvirion vaccine, or saline placebo. The rHA0 vaccines caused fewer local adverse reactions than did the commercial subvirion preparation. Neutralizing hemagglutinin-specific antibody responses to 15 micrograms of rHA0 were comparable to those elicited by licensed vaccine, not enhanced by the addition of alum, and significantly increased by raising the rHA0 dose from 15 to 90 micrograms. Compared with placebo recipients, rHA0-vaccinated subjects had significantly lower rates of influenza A (H3N2) virus infection and illness during the epidemic winter season. These results suggest that influenza vaccines containing purified rHA0 may offer an advantage over licensed preparations containing egg-grown antigens by inducing equivalent protective immune responses while being potentially less reactogenic.