This review analyses the recent literature devoted to two related fati
gue syndromes: chronic fatigue syndrome (CFS) and acute onset postvira
l fatigue syndrome (PVFS). The articles are grouped into five pathogen
ic tracks: infectious agents, immune system, skeletic muscle, hypothal
amo-pituitary-adrenal (HPA) axis and psychiatric factors. Although a p
articular infectious agent is unlikely to be responsible for all CFS c
ases, evidence is shown that host-parasite relationships are modified
in a large proportion of patients with chronic fatigue, Antibody titre
s against infectious agents are often elevated and replication of seve
ral viruses could be increased. Chronic activation of the immune syste
m is also observed and could be due to the reactivation of persistent
br latent infectious agents such as heroes viruses (i.e. HHV-6) or ent
eroviruses. It could also be favorised by an impaired negative feedbac
k of the HPA axis on the immune system, A model is proposed where the
abnormalities of the HPA axis are primary events and are mainly respon
sible for a chronic activation of the immune system which in turn indu
ces an increased replication of several viruses under the control of c
ellular transcription factors, These replicating viruses together with
cytokines such as TNF-alpha would secondarily induce functional disor
ders of muscle and several aspects of asthenia itself.