One of the first researchers to turn a paleopathological eye on Egyptian mummies was Sir Marc Armand Ruffer, who in his 1921 book "Studies of the Palaeopathology of Egypt" described three mummies with "dome shaped vesicles" extremely similar to those expected of smallpox [source: Ruffer]. The most ancient of these mummies was dated 1580 B.C.E., and the most recent was the mummy of Ramses V, who died in 1157 B.C.E.
After his own inspection of the mummy, Donald R. Hopkins, who participated in the World Health Organization's Smallpox Eradication Program, wrote of Ramses V, "Inspection of the mummy revealed a rash of elevated 'pustules', each about 2 to 4 millimeters in diameter, that was most distinct on the lower face, neck, and shoulders, but was also visible on the arms." [source: Hopkins]
Is this conclusive? No, not necessarily, and to date there has been no modern analysis of Ramses V that could definitively determine if his condition was, in fact, smallpox. But the circumstantial evidence seems strong.
Smallpox is one of history's greatest killers, responsible for 300 to 500 million deaths in the 20th century [source: Saint Louis University].