Vaccinia virus is a model virus for the study of the poxvirus family and forms the vaccine against smallpox. There are several membranes that envelope the vaccinia and smallpox viruses and on each membrane resides specific membrane proteins. The presence or absence of one or more membranes and its proteins leads to alternate forms of the infectious virus. Within two of these membrane forms are membrane proteins to which a vigorous immune response is mounted. We are studying two of these proteins from vaccinia with the use of biochemical techniques and the methods of x-ray crystallography. As the protein sequence similarity is very high between vaccinia and smallpox, the structures of vaccinia proteins should provide insight into the structures of proteins of the smallpox virus.