Several lines of evidence point to a possible relationship between vitamin D and cardiovascular disease. Animal experiments and observational studies in humans suggest vitamin D to be arteriotoxic and an association of high intake of vitamin D with increased incidence of ischemic heart disease (IHD). The major source of vitamin D in adults is vitamin D synthesized in the skin through exposure to the sun. In tropical environment there is a possibility of high level of solar exposure and enhanced serum levels of vitamin D in the population. We explored the relation between serum level of 25-hydroxyvitamin D3 and IHD in a case-control study involving 143 patients with either angiographic evidence of coronary artery disease or patients with acute myocardial infarction and 70 controls, all men in the age group of 45-65 years. Fasting blood samples were collected, serum separated and serum levels of 25-hydroxyvitamin D3 was measured by protein binding radioligand assay. Serum levels of cholesterol, triglyceride, calcium, magnesium and inorganic phosphate were also determined. Prevalences of diabetes, hypertension and smoking history were noted. Statistical comparisons of variables between cases and controls were done using chi2-tests. Multivariate logistic regression analysis was done to examine the association of IHD with serum levels of 25-hydroxyvitamin D3 controlling for selected variables. Serum levels of 25-hydroxyvitamin D3, calcium, inorganic phosphate, total cholesterol, low density lipoprotein and triglycerides were elevated in a higher proportion of patients, compared to controls. Serum levels of 25-OH-D3 above 222.5 nmol/l (89 ng/ml) was observed in 59.4% of cases compared to 22.1% in controls (p < 0.001; unadjusted odds ratio (OR): 5.17; 95% confidence interval (CI): 2.62-10.21). When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D3 levels (> or = 222.5 nmol/l, > or = 89 ng/ml) and IHD is 3.18 (95% CI: 1.31-7.73). Given the evidences for the arteriotoxicity of vitamin D, further investigations are warranted to probe whether the elevated serum levels of 25-hydroxyvitamin D3 observed in patients with IHD in a tropical environment has any pathogenic significance.