Abstract In a phase I clinical trial, one hundred healthy young adults were randomized to receive two doses 28 days apart of an inactivated, subvirion vaccine containing 15 or 45 μg of influenza A/H5N1 hemagglutinin (HA) by the intramuscular (IM) route, or 3 or 9 μg of H5 HA by the intradermal(ID) route. Seventy-seven subjects received a third dose. All regimens were safe and well tolerated. Antibody responses after two or three doses were low (≤20% or ≤38%, respectively) and similar in groups given 3 or 9 μg ID or 15 μg IM, and were significantly lower than those given 45 μg IM. Higher dosages of H5 HA and/or inclusion of adjuvant will be required to enhance immunogenicity by the ID route.