Objectives: To study the effects of two different mixtures of the main conjugated linoleic acid (CLA) isomers cis-9, trans-11 CLA and trans-10, cis-12 CLA on human immune function. Design: Double-blind, randomized, parallel, reference-controlled intervention study. Subjects and intervention: Seventy-one healthy males aged 31-69y received one of the following treatments: (1) mixture of 50% c9,t11 CLA and 50% t10,c12 CLA isomers (CLA 50:50); (2) mixture of 80% c9,t11 CLA and 20% t10,c12 CLA isomers (CLA 80:20); and (3) sunflower oil fatty acids (reference). The treatments were given as supplements in softgel capsules providing a total of 1.7 g (c9,t11 + t10,c12) CLA fatty acids (50:50) or 1.6 g (c9,t11 + t10,c12) CLA glycerides (80:20) per day in treatment groups for 12 weeks. Results: Almost twice as many subjects reached protective antibody levels to hepatitis B when consuming CLA50:50 fatty acids (15/24, 62%) compared with subjects consuming the reference substance (7/21, 33%, P=0.075). In subjects consuming CLA 80:20 glycerides this was 8/22 (36%). Other aspects of immune function, ie DTH responses, NK cell activity, lymphocyte proliferation and production of TNF-α, IL1-β, IL6, IFN-γ, IL2, IL4, and PGE2, were not affected. Conclusion: This is the first study that suggests that CLA may beneficially affect the initiation of a specific response to a hepatitis B vaccination. This was seen in the CLA 50:50, but not in the CLA 80:20 group. Chemicals/CAS: acylglycerol, 64706-27-0; gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; linoleic acid, 1509-85-9, 2197-37-7, 60-33-3, 822-17-3; prostaglandin E2, 363-24-6; sunflower oil, 8001-21-6; Dinoprostone, 363-24-6; Hepatitis B Antibodies; Hepatitis B Vaccines; Interferon Type II, 82115-62-6; Interleukins; Linoleic Acid, 2197-37-7; Tumor Necrosis Factor-alpha