Infection of turkeys with the haemorrhagic enteritis virus (HEV), a type II avian adenovirus, results in varying rates of morbidity and mortality. The disease is characterised by splenomegaly, intestinal haemorrhage, sudden death and immunosuppression. The mechanisms of HEV immunopathogenesis and immunosuppression are not fully understood. Recent studies indicate that immune responses play a central role in disease pathogenesis. HEV infects B cells and macrophages and induces necrosis as well as apoptosis in infected and possibly in by-stander cells. The ability of the infected birds to mount an optimum humoral immune response as well as normal macrophage functions such as phagocytosis may be impaired. Elevated numbers of splenic CD4(+) cells during the acute phase of infection may be associated with viral clearance. Types I and II interferons (IFN) and pro-inflammatory cytokines such as interleukin-6 and tumour necrosis-like factors (TNF) are released at the peak of the infection. Cytokines may play a protective as well as a destructive role. While a massive release of proinflammatory cytokines may lead to systemic shock associated with haemorrhagic enteritis and death, release of IFNs may protect turkeys from the disease. Treatment with thalidomide, which is a potent TNF down-regulatory drug, prevented HEV-induced intestinal haemorrhage and treatment with an IFN-inducing chemical prevented HEV-replication and inhibited HEV-induced pathological and histopathological lesions.