Measurements of the acute phase proteins, C-reactive protein (CRP) and orosomucoid are widely used to monitor the activity of Crohn's disease. The effect of TPN upon the levels of acute phase proteins is unknown. Serum levels of CRP and orosomucoid were measured simultaneously over a four year period in 13 patients receiving TPN for Crohn's disease, nine patients with noninflammatory causes of intestinal failure, and 16 patients with Crohn's disease treated without TPN. An acute phase response was found with a similar frequency in both groups of patients with Crohn's disease (73.6% and 83.9% for Crohn's with and without TPN respectively), but was less prevalent in patients receiving TPN for non-inflammatory causes of intestinal failure (56.1%, P < 0.01). In this latter group, the acute phase response consisted primarily of an isolated elevation of orosomucoid (78.4%), compared with patients with Crohn's disease alone (21.1%, P < 0.001) and with Crohn's disease and TPN (46.6%, P < 0.05). Liver function abnormalities were seen on 68.8% of occasions in patients with noninflammatory causes of intestinal failure who had elevated levels of orosomucoid, compared with 34.9% of occasions on which orosomucoid levels were normal (P < 0.001). TPN may lead to isolated elevation of serum levels of orosomucoid, reducing the value of this acute phase protein in monitoring the activity of Crohn's disease in patients receiving TPN.