The aetiopathology of atherosclerosis remains obscure. Although histologically the accumulation of lipids and the proliferation of the smooth muscle cells represents the main feature of the disease, little is known as regards the molecular alterations associated with the atherosclerotic lesions. In the present study we investigated whether an elevated mutational rate is detectable in human atheromatous plaques. Thirty specimens were assessed for microsatellite instability (MI) by 7 microsatellite markers and MI, in at least one marker, was apparent in 6 (20%) cases. Our data suggest that decreased fidelity in DNA replication and repair may be associated with the development of the disease.