Previous studies have implicated oestrogen as a factor in the induction of fatty liver haemorrhagic syndrome (FLHS). In this study a refined laying hen model was employed to permit further investigations. Intramuscular (i.m.) injections of exogenous oestrogen as β-estradiol-17-dipropionate (E₂) (5mg/kg BW) were given every 4 days for 20 days to 30 week old hens fed either ad libitum or with restricted feed intake. Elevated (P < 0.01) plasma oestrogen concentrations produced significant hepatic macroscopic and microscopic alterations. Hens in the E₂-treated ad libitum fed (EAL) group experienced a higher incidence of FLHS than hens in the E₂-treated restricted feed intake (ERF) group, showing that birds with a higher feed intake are more at risk of developing FLHS. Histological examination of livers, revealed that hens in the EAL group had consistent and severe fat infiltration in the liver, and fat vacuolisation within hepatocytes. Fat accumulation and fat droplets were found not only in the cytoplasm of hepatocytes, but also in liver sinusoids. White blood cell (WBC) counts and fibrinogen concentrations were altered (P < 0.01) in hens treated with E₂ when compared with controls. Plasma fibrinogen concentrations were altered over time, and correlated with WBC counts (Pearson's correlation r=0.96; P=0.001). Hens treated with E₂ had increased (P < 0.01) levels of cholesterol (CHOL) and triglycerides (TG), confirming that E₂ induced hypercholesterolemia and hypertriglyceridemia. It was concluded that, E₂ successfully induced FLHS in hens, with typical systemic and hepatic events resulting from a disturbance in lipid metabolism and chronic low-grade inflammation.