Objectives: This study investigated the effect of dietary CLA supplementation (3g/day; 50:50 mix of the two major isomers) on the immune system and plasma lipids and glucose of healthy human (male and female) volunteers. Design: Double-blind, randomized, reference-controlled study. Subject and intervention: A total of 28 healthy male and female participants aged 25-50 y received either high oleic sunflower oil (reference) or 50% CLA 9-11 and 50% CLA 10-12 CLA isomers (50:50 CLA-triglyceride form). The treatments were given as supplements in soft-gel capsules providing a total 3 g (6 Â 500 mg capsules) per day in treatment groups for 12 weeks. A 12-week washout period followed the intervention period. Results: Levels of plasma IgA and IgM were increased (Po0.05 and 0.01 respectively), while plasma IgE levels were decreased (Po0.05). CLA supplementation also decreased the levels of the proinflammatory cytokines, TNF-a and IL-1b (Po0.05), but increased the levels of the anti-inflammatory cytokine, IL-10 (Po0.05). Another aspect of immune function, delayed type hypersensitivity (DTH) response, was decreased during and after CLA supplementation (Po0.05). However, plasma glucose, lipids, lymphocyte phenotypic results were not affected significantly by CLA. Conclusion: This is the first study to show that CLA, a fatty acid naturally found in dairy and meat products, can beneficially affect immune function in healthy human volunteers. Sponsorship: This study was supported by Loders-Croklaan, The Netherlands and SEERAD (Scottish Executive Environmental Rural and Agriculture Department).