Four antigenic sites, each capable of undergoing independent antigenic alterations, have been delineated on the hemagglutinin molecule of influenza virus A/PR/8/34. The sites Sa and Sb contain mostly "strain-specific" epitopes whereas sites Ca and Cb contain predominantly "cross-reactive" epitopes. Thus, antigenic drift occurred in nature to a much larger extent in the sites Sa and Sb than in the sites Ca and Cb. Sites Sa, Sb and Ca may be close to the tip of the HA spike while site Cb may be located more towards the base of the spike. Anti-Sa and anti-Cb antibodies bind noncompetitively to the HA molecule. The four sites are formed exclusively or predominantly by the HA1 polypeptide. Analysis of virus infected P815 cells by means of hybridoma antibodies has shown that internal viral proteins (M and NP) are present in addition to viral glycoproteins on the external cell surface. M protein is present in very small quantities (approx. 5000 molecules/cell). NP is present at roughly 10-fold higher concentration than M protein. Low levels of Cr-release from Cr-labelled virus infected cells is mediated by anti-NP antibodies plus complement but not by anti-M antibodies.