The influenza hemagglutinin has been isolated from the capsid and a proteolytic cleavage (producing the B-Ha subdomain) can separate it from the viral envelope membrane in a soluble form. At neutral pH, the protein can be mixed with phospholipid vesicles, with no apparent interaction. At low pH, however, the viral peptide undergoes a conformational change which causes a new hydrophobic surface to be exposed. This leads to interaction with or insertion into the phospholipid vesicles and mimics the physiological reaction of viral entry into the cell. We have observed this interaction in frozen, hydrated vesicles of B-Ha at pH 5. There are many protein molecules packed closely on the surface of the vesicles. The protein appears to insert at least part of the way through the vesicle. It extends in an elongated density perpendicular to the surface for about 100 _, and terminates in a bulb or club-shaped tip. We will extend these studies to explore the feasibility of making 2-D crystals of the B-Ha. The X-ray structure of the low and high pH forms is known for various parts of the molecule, but not for the entire protein in its membrane-active form. The EM studies will fill in this gap and test the various hypotheses for the conformational change that is thought to accompany and facilitate the viral cell entry.