Surveillance for influenza A virus infection of seals has continued following the association of influenza A virus with epizootics of pneumonia in seals off the New England coast in 1979–1980 and 1982–1983. In January 1991 and January to February 1992, influenza A viruses were isolated from seals that died of pneumonia along the Cape Cod peninsula of Massachusetts. Antigenic characterization identified two H4N6 and three H3N3 viruses. This was the first isolation of H3 influenza viruses from seals, although this subtype is frequently detected in birds, pigs, horses and humans. Haemagglutination inhibition assays of the H3 isolates showed two distinct antigenic reactivity patterns: one more similar to an avian reference virus (A/Duck/Ukraine/1/63) and one more similar to a human virus (A/Aichi/2/68). The haemagglutinin (HA) genes from two of the H3 seal viruses showing different antigenic reactivity (A/Seal/MA/3911/92 and A/Seal/MA/3984/92) were 99.7% identical, with four nucleotide differences accounting for four amino acid differences. Phylogenetic analysis demonstrated that both of these sequences were closely related to the sequence from the avian H3 virus, A/Mallard/New York/6874/78. This indicates that influenza A viruses of apparent avian origin, including the H3 subtype viruses, continue to infect seals.