In this study, we proposed a new medical diagnosis system based on principal component analysis (PCA), k-NN based weighting preprocessing, and Artificial Immune Recognition System (AIRS) for diagnosis of atherosclerosis from Carotid Artery Doppler Signals. The suggested system consists of four stages. First, in the feature extraction stage, we have obtained the features related with atherosclerosis disease using Fast Fourier Transformation (FFT) modeling and by calculating of maximum frequency envelope of sonograms. Second, in the dimensionality reduction stage, the 61 features of atherosclerosis disease have been reduced to 4 features using PCA. Third, in the pre-processing stage, we have weighted these 4 features using different values of k in a new weighting scheme based on k-NN based weighting pre-processing. Finally, in the classification stage, AIRS classifier has been used to classify subjects as healthy or having atherosclerosis. Hundred percent of classification accuracy has been obtained by the proposed system using 10-fold cross validation. This success shows that the proposed system is a robust and effective system in diagnosis of atherosclerosis disease. (C) 2007 Elsevier Inc. All rights reserved.