Proteins from grossly and histologically normal human aortic intimas and human aortic intima with fatty streaks or fibro-fatty lesions were extracted with 9 M urea mixture. Protein extracts were mixed with an internal absorbance calibrator (carbonic anhydrase) and subsequently separated by two-dimensional gel electrophoresis, silver stained, and quantitated by a laser beam densitometer. The vascular-origin proteins actin, tropomyosin-like proteins, tubulin, glycoprotein G35, and two myosin light chains were present in the highest amounts in normal aortic intima (27-year-old male). Quantitation of vascular-origin proteins in aortic intima with a fibro-fatty lesion from the same subject showed a slight decrease in relative amount of these proteins as compared to the normal intima. Several polypeptides (P15, P18, P60, P110b) and plasma-derived proteins not observed in the normal intima were found in fibro-fatty lesion (albumin, haptoglobin beta-chain, fibrinogen beta-chain, alpha 1-HS-glycoprotein). Other proteins which were present in very low amounts in the normal intima (transferrin, alpha 1-antitrypsin, apolipoprotein A-1, P56, P190) were found to be major proteins of intima with fibro-fatty lesion. Differences in relative amount of plasma-derived and vascular-origin proteins between normal intima and intima with fatty streaks, studied in a large number of specimens from 38 thoracic intimas and 18 paired abdominal intimas (16-34 years old) were less prominent. Statistically significant increases of the albumin/actin ratio were found in fatty streaks as compared to paired normal intimas as well as in the mean value of albumin/actin ratio in the group of fibro-fatty lesions (mean = 6.1) as compared to the group of fatty streaks (mean = 1.7) or normal intima (mean = 0.7). Several lesion unique proteins were observed; however, the frequency of the occurrence of these proteins in 41 specimens with lesion was low. No significant differences were observed in intima protein pattern and quantities of selected intima proteins between paired thoracic and abdominal aortas.