Intake of fruits and vegetables has been related to lower risk of ischaemic stroke, but the nutrients responsible for this apparent benefit remain ill-defined. Tocopherols (vitamin E) have also been proposed to be protective. Dutch researchers conducted a prospective, nested case-control analysis among male physicians without diagnosed cardiovascular disease followed-up for up to 13 years in the Physicians’ Health Study. Samples from 297 physicians with ischaemic stroke were analysed with paired controls, matched for age and smoking, for five major carotenoids (alpha- and beta-carotene, beta-cryptoxanthin, lutein and lycopene), retinol, and alpha- and gamma-tocopherol. Baseline plasma levels of alpha-carotene and beta-carotene and lycopene tended to be inversely related to risk of ischemic stroke with an apparent threshold effect. As compared with men whose plasma levels were in the lowest quintile, the multivariate adjusted ORs of ischaemic stroke among men with levels in the second to the fifth quintiles were 0.59 (95% CI 0.36 to 0.98) for alpha-carotene, 0.62 (95% CI 0.38 to 1.01) for beta-carotene, and 0.61 (95% CI 0.37 to 1.00) for lycopene. A tendency to an inverse association was found for beta-cryptoxanthin, but the result was not statistically significant. No association was found for lutein, retinol and tocopherols.