Conjugated linoleic acid (CLA) refers to geometric and positional isomers of linoleic acid. Animal studies have shown that CLA modulates the immune system and suggest that it may have a therapeutic role in inflammatory disorders. This double-blind placebo-controlled intervention trial investigated the effects of CLA supplementation on indices of immunity relating to cardiovascular disease (CVD) in a cohort of healthy middle-aged male volunteers. Subjects were randomly assigned to supplement their diet with 2.2 g 50:50 isomeric blend of cis 9, trans 11 (c9, t11)-CLA and trans 10, cis 12 (t10, c12)-CLA or placebo daily for 8 weeks. Interleukin (IL) 2, IL-10 and tumour necrosis factor (TNF) alpha were measured in the supernatant of cultured unstimulated and concanavalin A (Con A)-stimulated peripheral blood mononuclear cells (PBMC) by ELISA. Serum IL-6 and plasma CRP were measured by ELISA and plasma fibrinogen by automated clotting assay. Gene expression was investigated by real-time RT-PCR. CLA supplementation significantly reduced Con A-stimulated PBMC IL-2 secretion (37.1%; P=.02). CLA supplementation had no significant effect on transcription of IL-2. CLA supplementation had no direct significant effects on PBMC TNFalpha or IL-10 secretion. Other inflammatory markers associated with CVD, including IL-6, CRP and fibrinogen, were not affected by CLA supplementation. This study showed that CLA supplementation reduced PBMC IL-2 secretion from Con A-stimulated PBMC but lacked effect on other markers of the human inflammatory response.