Semicarbazide sensitive amine oxidase (SSAO) metabolizes oxidative deamination of primary aromatic and aliphatic amines. It is selectively expressed in vascular cells of blood vessels, but it is also circulating in blood plasma. SSAO activity in plasma is increased in some diseases associated with vascular complications and its catalytic products may cause tissue damage. We examined the effect of the oxidation of the SSAO substrate, methylamine, on cultured smooth muscle cells. Cell incubation with methylamine plus soluble SSAO, contained in bovine serum, resulted toxic to rat aorta A7r5 and human aortic smooth muscle cells, as measured by MTT reduction. This effect was completely reverted by specific SSAO inhibitors, indicating that the toxicity was mediated by the end products generated. Moreover, SSAO-mediated deamination of methylamine induced apoptosis in A7r5 cells, detected by chromatin condensation, Caspase-3 activation, PARP cleavage and cytochrome c release to cytosol. Formaldehyde, rather than H2O2, resulted to be a strong apoptotic inducer to A7r5 cells. Taken together, the results suggest that increased plasma SSAO activity in pathological conditions, could contribute to apoptosis in smooth muscle cells, leading to vascular tissue damage.