613 Cardiac allograft vasculopathy (CAV) is the major limitation to long term survival following orthotopic heart transplantation (OHT). Plasma homocysteine may contribute to CAV due to its role as a risk factor in other vascular diseases. We prospectively examined plasma homocysteine levels in 17 cardiac transplant patients prior to and 6 months following OHT using a validated HPLC method with fluorescence detection. Changes in homocysteine concentration were also compared to creatinine, cyclosporine (CsA) concentration, CsA dose, and prednisone dose. All patients received CsA, azathioprine and prednisone maintenance immunosuppressive therapy. Lymphocytolytic induction therapy was not used. The mean age of the study population was 51±14 years and 94% were male. Ischemic cardiomyopathy was present in 8 patients (47%). The mean homocysteine concentration increased from a pretransplant concentration of 21.7±9.5 mmol/L to a 6 month concentration of 25.0±13.6 mmol/L(p=NS). An average percent increase of 66% was observed in 9 (53%) patients after 6 months, while 8 (47%) patients demonstrated a 21% decrease in homocysteine concentration at 6 months. A significant increase in pretransplant creatinine was observed during the same 6 month period, 1.5±.50 versus 2.1±.81 mmol/L (p=0.008). Linear regression analysis showed a significant correlation between plasma homocysteine and serum creatinine concentrations (r=0.6210, p<0.0001). No relation was found between the increase in homocysteine concentration, CsA concentration, CsA dose, and prednisone dose. Conclusion: An increase in homocysteine concentration was observed in over half of the patients within 6 months following OHT. Homocysteine concentration appears to correlate with serum creatinine, but not with CsA concentration, CsA dose, or prednisone dose. Future prospective studies will need to determine the significance of elevated homocysteine following OHT in this subgroup of patients and their risk for CAV and other cardiovascular events.