· David Duchovny - Agent Fox William Mulder (1993–2001, 2002)
· Gillian Anderson - Agent Dana Katherine Scully (1993–2002)
· Mitch Pileggi - Director Asistente Walter S. Skinner (1994–2002)
· William B. Davis - C.G.B. Spender, El Fumador (1993–2000, 2002)
· Nicholas Lea - Alex Krycek (1994–1996, 1998–2002)
· Chris Owens - Jeffrey Spender (1998–1999, 2002)
· James Pickens, Jr. - Director Alvin Kersh (1998–2002)
· Robert Patrick - John Doggett (2000–2002)
· Annabeth Gish - Monica Reyes (2001–2002)
· Tom Braidwood - Melvin Frohike (1994–2002)
· Dean Haglund - Richard "Ringo" Langly (1994–2002)
· Bruce Harwood - John Fitzgerald Byers (1994–2002)
· Charles Cioffi - Jefe Scott Blevins (1993, 1997)
· Jerry Hardin - Garganta Profunda (1993–1996, 1999)
· John Neville - El Hombre Bien Arreglado (1995–1998)
· Steven Williams - Sr. X (1994–1997, 2002)
· Laurie Holden - Marita Covarrubias (1996–2000, 2002)
· Don S. Davis - Bill Scully (1994)
· Melinda McGraw - Melissa Scully (1994–1995, 1997)
· Sheila Larken - Margaret Scully (1994–1997, 2001–2002)
· Brian Thompson - Cazador Extraterrestre (1995–1996, 1998–2000)
· Brendan Beiser - Agente Pendrell (1995–1997)
· Rebecca Toolan - Teena Mulder (1995–1997, 1999–2000)
· Peter Donat - William Mulder (1995–1996, 1999)
· Floyd "Red Crow" Westerman - Albert Hosteen (1995, 1999)
· Don S. Williams - El Primer Anciano (1995–1999)
· Pat Skipper - Bill Scully, Jr. (1997)
· Karri Turner - Tara Scully (1997)
· John Finn - Michael Kritschgau (1997, 1999)
· Jeff Gulka - Gibson Praise (1998, 2000, 2002)
· Veronica Cartwright - Cassandra Spender (1998–1999)
· Mimi Rogers - Diana Fowley (1998–1999)
· Michael McKean - Morris Fletcher (1998–1999, 2002)
· Adam Baldwin - Knowle Rohrer (2001–2002)
· Cary Elwes - Director Asistente Brad Follmer (2001–2002)
· James & Travis Riker - Bebé William (2001–2002)