The deregulation of homocysteine metabolism leads to hyperhomocysteinemia, a condition described as an independent cardiovascular disease risk factor. Ubiquitous plasma membrane redox systems can play a dual pro-oxidant and anti-oxidant role in defense. In this study, we test the hypothesis that homocysteine, as a redox active compound, could modulate the endothelial plasma membrane redox system. We show that homocysteine behaves as a very potent stimulator of this activity. Furthermore, we show that this inducing effect is also produced on tumor cells and that it can be observed at both the activity and protein levels. On the other hand, homocysteine treatment decreases the activity of the specific ectocellular tumor NADH oxidase. Taken together, these results underscore a potential antitumoral action of homocysteine.