A comparative study of biological properties of natural and plasmid human interferons was carried out. Natural and leukocyte interferons: alpha (induced by Newcastle disease virus) and gamma (induced by staphylococcal enterotoxin A) as well as natural fibroblastic beta interferon induced by poly(I) X poly(C) were studied in comparison with plasmid interferons alpha-F and alpha-F/D obtained from recombinant bacteria. Antigenic determinants of plasmid interferons alpha-F and alpha-F/D were found to be identical with those of natural and alpha-interferon of man and to differ from those of natural human alpha- and beta-interferons. Both plasmid interferons demonstrated the kinetics of development of the state of resistance to viruses in a human diploid cell culture typical of alpha-interferon but not of gamma-interferon from human leukocytes. Plasmid and natural alpha-interferons have similar anticellular activity for human tumor HeLa cells, similarly activate natural human killer cells and are similarly stabilized in the presence of 0.01 M lantan chloride. All these data permit a conclusion that plasmid human interferons alpha-F and alpha-F/D are analogous and close to the total preparation of natural alpha-interferon from human leukocytes. On the other hand, the range of cells sensitive to the antiviral effect of alpha-F and alpha-F/D interferons is wider than for leukocyte alpha-interferon, and stability on storage and heating is higher.