Serien følger to FBI-agenter – Fox Mulder, spillet af David Duchovny, og Dana Scully, spillet af Gillian Anderson – i deres undersøgelser af usædvanlige sager, der ofte er af en paranormal natur. F.eks. sager om folk, der er blevet bortført af rumvæsener, eller folk der har været i kontakt med overnaturlige mennesker og andre skabninger.

A recently unearthed repository of materials formerly classified by the secret government....The Phenomenon Archives.

This series covers the taboo subjects which have had light shed on them by pouring over the materials in this repository.

Set within a hospital, located on the outskirts of town, mysterious phenomenons occur in sequence around a nurse. The nurse is suspected as the cause for some horrible cases and finds herself in danger.