Two monoclonal antibodies (MAbs) have been isolated that bind to human P450 2D6 and inhibit 2D6 catalyzed bufuralol 1-hydroxylation by 90%. One but not both of the MAbs immunoblotted 2D6. The MAbs were highly specific to 2D6 and did not cross-react with other P450s. Inhibitory monoclonal antibodies will be useful for determining the contribution of 2D6 to the metabolism of a wide variety of 2D6 and other P450 substrates in human tissues containing multiple P450s.