Indoleamine 2,3 dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, suppresses T cell activity and is up-regulated by various inflammatory stimuli. The ratio of kynurenine, the main metabolite of tryptophan, to tryptophan (kyn/trp) reflects IDO activity. We calculated IDO activity and measured carotid intima-media thickness (IMT), a presymptomatic predictor of atherosclerosis, in 986 young adults (544 female, 442 male) for whom data on levels of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, high sensitive C-reactive protein (CRP), body mass index (BMI), waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure and smoking habits were available. IDO activity correlated significantly with IMT in female subjects, but not in males. In a multivariate linear regression model, IDO did not correlate independently with IMT in female subjects. However, IDO activity correlated significantly with several risk factors for atherosclerosis in females, i.e. with age, LDL-C, BMI, weakly with CRP and inversely with HDL-C and triglyceride. In males IDO activity correlated significantly with CRP and inversely with HDL-C. In conclusion, our results suggest that the IDO enzyme is involved in the immune regulation of early atherosclerosis, particularly in young female adults, and could constitute a novel marker of immune activation in early atherosclerosis in females.