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Hyperhomocysteinemia is an independent risk factor for coronary disease and elevated plasma homocysteine levels have been documented in heart transplant recipients. The aim of this study was to test the hypothesis that homocysteine levels are associated with presence or absence of transplant coronary artery disease.Forty-three non-smoking adults were recruited, all of whom had received a heart transplant between 2 and 7 yr previously. All 43 had blood drawn for fasting homocysteine level on the day of presentation. All patients had undergone diagnostic coronary angiography within the past 6 months.For all patients, the average fasting plasma homocysteine level was 17.0 ± SD 6.6 μmol/L with a range from 6.0 to 36.9 μmol/L. Twenty-six patients (60%) had fasting plasma homocysteine levels above 15.0 μmol/L. On the basis of arteriography, patients were categorized as those with angiographically normal (n = 22) or abnormal (n = 21) coronary arteries. There was no difference in the mean plasma homocysteine level comparing patients with angiographically normal (17.2 ± SD 7.0 μmol/L) to those with abnormal (16.8 ± SD 6.2 μmol/L) coronary arteries. Plasma homocysteine levels increased with increasing plasma creatinine levels (r = 0.63, p < 0.0001) and with decreasing vitamin B6 levels (r = −0.56, p < 0.0001).Mild hyperhomocysteinemia is a consistent finding among heart transplant recipients. This finding was not associated with transplant coronary artery disease in our patients. The combination of renal dysfunction and vitamin B6 deficiency may explain the unusual prevalence of hyperhomocysteinemia in heart transplant recipients.