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A high plasma homocysteine concentration is a risk factor for atherosclerosis and thrombosis, which are major causes of morbidity and mortality in heart transplant patients. High homocysteine concentrations may be caused by lower folate and vitamin B6 levels. We hypothesized that these patients might have high homocysteine concentrations and low levels of folate and vitamin B6, which could contribute to the development of vascular complications.Total fasting plasma homocysteine was measured in 189 cardiac transplant recipients and in healthy controls, as were concentrations of folate, vitamin B12, vitamin B6, and creatinine.Homocysteine concentrations were higher in recipients than controls(19.1±13.0 vs. 11.0±3.0 μmol/L,P<0.01), and hyperhomocysteinemia (>90th percentile for controls, 14.6 μmol/L) was seen in 68% of recipients(P<0.01). Folate and vitamin B6 concentrations were lower (5.9±4.2 vs. 7.9±4.2 pmol/L and 40±25 vs. 84±77 nmol/L, respectively; P<0.01 for both). Folate and vitamin B6 deficiencies were seen in 10.8% and 17.9% of recipients, respectively (P<0.01). Hyperhomocysteinemia was more frequent in patients with vascular complications after transplantation than in those without (79.2% vs. 63.8%,P<0.05).Elevated plasma homocysteine and deficiencies of folate and vitamin B6 are common in transplant recipients. A high homocysteine concentration was more common in patients with vascular complications. Prospective studies are now required to evaluate the role of these abnormalities as risk factors for the atherothrombotic complications of transplantation.