General John P. Jumper, then Chief of Staff of the Unites States Air Force, was to make his second cameo appearance in this episode to make the speech at the hangar, but at the last minute he was unavailable. Don S. Davis stood in as General Hammond to deliver the same speech at short notice, which is why he is wearing a civilian suit rather than a uniform.
The producers had hoped to bring back Sean Patrick Flanery as Orlin however he was unavailable. Instead the role was rewritten as a young Orlin.
The "Dark Pariah" song Dr. Lee is using to test frequencies is "Infinity" by Robert J. Walsh, Dennis Winslow and Ronn L. Chick, from their album "Deutsch Rock And Metal Angst" (aka "Hollywood Music").
Although he receives "Special Guest Star" billing, Julian Sands (The Doci) only appears in footage from Origin (2005).
Bill Dow (Dr. Bill Lee) previously appeared in an episode of Millennium (1996) with the same title: The Fourth Horseman (1998). Both episodes involve the outbreak of a terrible disease.