Three group of children were immunized with an inactivated Port Chalmers (H3ChN2Ch) influenza vaccine (group A), a neuraminidase-specific (HeqlN2Ch) influenza vaccine (group B), or a placebo. Immunization induced seroconversion for H3Chand N2Ch-specific antibody in group A and for N2Ch antibody in group B. The protective efficacies observed against naturally acquired illness with the Port Chalmers strain of influenza A virus were 68.7% and 37.4% in groups A and B, respectively, in comparison to the placebo group, and those against illness produced by the subsequent outbreak of the Victoria strain were 80.0% and 72.7%. These data support the role of neuraminidase-specific immunization in protection against influenza. Although the degree of protection after vaccination with the HeqlN2Ch vaccine was less than that provided by the biphasic H3ChN2Ch vaccine against the Port Chalmers strain, it appeared to be similar in the two vaccine study groups against the Victoria strain.