Novel two-dimensional (21)) cross-linked polysiloxane LB films were prepared and applied to nitric oxide (NO)-permselective films in order to block other electroactive interfering substances, such as L-ascorbic acid, L-cysteine, and acetaminophen. The 2D cross-linked siloxane LB films deposited on Pt electrodes were remarkably effective in the elimination of the interfering responses and a rapid response to NO remained with modified LB films consisting of monolayers or even several layers.