Crohn's disease is associated with osteoporosis, malnutrition and altered function of peripheral blood mononuclear cells (PBMC). The responses of circulating immune cells and extra-intestinal manifestations to increased inflammatory activity and to modulation by dietary supplementation are uncertain. The relationships between disease status, bone turnover and body mass and composition, PBMC function and fatty acid availability have been investigated in patients with Crohn's disease. The availability of n-3 and n-6 PUFA is altered in adult patients and interferon (IFN)-γ production by PBMC is lower. Increased inflammatory activity is associated with increased bone resorption in adult patients and decreased body mass in paediatric patients. In healthy male subjects there is a proportionate relationship between supplementary intake of EPA and DHA (0.3–2.0 g as fish oil/d) in combination with antioxidants (vitamins A, C and E and Se) and incorporation into plasma phospholipids and PBMC, and a non-linear relationship with PBMC synthesis of TNF-α, IL-6 and prostaglandin E2 (decrease) and IFN-γ (increase). In adults with Crohn's disease high-dose fish oil (2.7 g EPA+DHA/d) in combination with antioxidants (vitamins A, C and E and Se) increases the EPA and DHA content of PBMC and decreases the production of IFN-γ by PBMC, but is not associated with effects on bone turnover or nutritional status.