The apolipoprotein E (APOE) gene is located on chromosome 19, and the three most common alleles are designated ε2, ε3, and ε4. The ε4 allele is associated with atherosclerosis, cardiovascular disease, Alzheimer disease, and decreased longevity. Recently a decreased antioxidant activity of the ε4 allele was demonstrated. In our aim to identify genetic risk factors for the development of left ventricular failure (LVF) inβ-thalassaemia homozygotes, which is not explained by the secondary haemosiderosis only, we studied the APOE allele distribution in such patients compared with controls. The material consisted of 42 patients with homozygousβ-thalassaemia and LVF, 67 patients with homozygous β-thalassaemia without heart failure, as compared to a control sample of 216 healthy blood donors. The frequency of allele ε4 in patients with LVF (14.3%) was significantly higher than in controls (6.5%, χ2=5.99, p<0.05). In patients without heart failure there was no significant difference in APOE allele distribution compared with controls. We suggest that APOE alleleε4 is a risk factor for development of LVF in β-thalassaemia homozygotes. If these preliminary findings are confirmed in bigger materials, it will be of big importance for early intervention in patients with predisposition to LVF.