A series of trials was conducted in which wild-type A/USSR/90/77 (H1N1) influenza A virus and a few of its antigenic variants were inoculated into volunteers. Infections readily occurred in people of all ages who had initial low antibody titers, but clinical effects were generally mild in comparison with those of the previously tested subtypes, H0N1, H1N1, H2N2, H3N2. There was, however, an inverse relationship between severity of symptoms and age of volunteers, although the incidence of virus excretion and of increase in anti-hemagglutinin was apparently not age related. Naturally occurring recombinant viruses with H3 hemagglutinin and one or more genes of A/USSR/098/77-like strains were likewise studied in volunteers. These clones also produced mild symptoms, providing evidence of an attenuating effect on H3N2 viruses by the substitution of some of its genes with the genes of an H1N1 virus.