A selective, derivative spectrophotometric method has been developed for the determination of malonaldehyde (MLD), based on a reaction with 2-thiobarbituric acid (TBA). The proposed method has been applied to the determination of MLD in human plasma. A study to eliminate several spectral interferences is described. A comparative study of the results obtained using the proposed derivative method and a conventional TBA method applied to human plasma is presented and the advantages of the proposed method over the conventional method for the determination of MLD in human plasma are evaluated.