Moderate hyperhomocysteinaemia has been shown to constitute an independent risk factor for cardiovascular disease (CVD), a frequent cause of morbidity and mortality in renal transplant recipients (RTR). In these patients few data regarding both total homocysteine levels and their influence on cardiovascular risk have been reported. We therefore studied serum homocysteine levels in deep-frozen sera from 42 kidney transplant recipients with a follow-up of 11 +/- 4.5 years (mean +/- SD) after transplantation. Eighteen patients had one or more ischaemic events (CVD (+)) and 24 patients had none (CVD (-)). Serum samples had been drawn 1-6 months prior to the first vascular event in CVD (+) patients and serum storage time was comparable in both CVD (-) and CVD (+) patients. Serum homocysteine levels were measured using a radioenzymatic method. Mean homocysteine level was significantly higher in 42 RTR males and females (15.5 +/- 6.3, 13.5 +/- 5.5 microM respectively) compared with 35 control subjects matched for age and sex (8.7 +/- 1.9, 7.5 +/- 1.9 microM, P < 0.001). The difference in serum homocysteine levels between CVD (+) and CVD (-) RTR nearly reached statistical significance in male patients (18.6 +/- 7.8 versus 13.1 +/- 3.4 microM, P < 0.06) but not in female patients (P = NS). In the CVD (+) group 11/18 patients had homocysteine levels > 14 microM (the upper limit in healthy controls) versus 7/24 in the CVD (-) group (P = 0.04). In these patients we simultaneously measured in the same serum samples, serum triglycerides, and total and HDL cholesterol, and calculated LDL cholesterol. By stepwise discriminant analysis and by logistic regression analysis in this relatively small patient population, only serum triglycerides and homocysteine were selected as risk factors associated with CVD. We conclude that significant hyperhomocysteinaemia is present in renal transplant recipients and represents a potential risk factor for cardiovascular disease in these patients.