In this work, we have studied the amino acid and protein composition of the plasma from a group of 32 ALS patients. As controls, groups of 10 healthy subjects (HC) and 32 patients with other neuromuscular disorders have been analysed. When the HC group was compared with the ALS group there were significant decreases of His (39+/-18 to 24+/-9 microM, p<0.01) and Ala (313+/-62 to 237+/-66 microM, p<0.05), and a significant increase of Asn (89+/-41 to 118+/-24 microM, p<0.05), for the ALS group. When the three groups were compared, we observed significant decreased concentrations of Ser, His, Thr, Ala, Arg, Tyr, Met, Cys, Ile, and significant increases of Asn, Phe and Lys. An increase of proteolytic products of alpha2-macroglobulin (alpha2-M), an acute-phase serum glycoprotein that functions as a protease inhibitor, has been observed for a subgroup of ALS patients by Western blot. Furthermore, the detection of alpha2-M during disease progression has shown increases of the intact subunit and of a proteolytic product for two of the four patients analysed. Another acute-phase glycoprotein, haptoglobin, which regulates haemoglobin degradation, was not increased for the same group of patients. The results obtained suggested that diet supplementation with His and Ala and modulation of alpha2-M might have some beneficial effects on the course of ALS.