Lactic acidosis resulting from excessive fermentation of starch by ruminants can lead to many deleterious effects on the animal including shock and death in severe cases. The exact mechanisms mediating this response are still relatively unknown and the present study has examined the influence of lactic acidosis in sheep on the production of tumour necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine. Lactic acidosis was induced in 6 Merino sheep by feeding 2 kg of barley-based pellets. Lactic acid levels rose in rumen fluid and faeces from 0.5 to 32.1 mmol/L and 0.5 to 48.0 mmol/L, respectively (P < 0.05); whereas, pH in both rumen fluid and faeces decreased from 8.22 to 5.18 and 7.05 to 5.00, respectively (P < 0.05), after lactic acidosis. TNF-α levels increased in faeces from 15 ng/g to 75 ng/g (P < 0.05) 24 h and 12 h after ruminal and hind gut lactic acidosis incidence, respectively. These preliminary findings suggest the possibility of an immune response in the body to lactic acidosis indicated by increasing TNF-α levels. TNF-α may be a mediator of lactic acidosis and its presence may explain many of the secondary effects observed after acidosis including laminitis and liver abscesses.