Dialysis arthropathy is the most prominent dialysis-related amyloidosis feature. Alpha-1-antitrypsin (alpha-1-proteinase inhibitor) is the major circulating antiprotease. Twenty-three otherwise uncomplicated hemodialysis patients with well-documented dialysis arthropathy had a significantly (p < 0.05) lower serum mean concentration, 1,960 +/- 410.4 mg/l of alpha-1-antitrypsin than 47 patients with no joint symptoms who had a mean concentration of 2,256.6 +/- 424.5 mg/l. Decreased levels of the substance were detected in 13 (56.5%) of the 23 patients with dialysis arthropathy and in 13 (27.6%) of those 47 with no joint symptoms, the incidence in the former group being significantly (p < 0.05) higher than in the latter. In the dialysis arthropathy group, serum alpha-1-antitrypsin levels correlated inversely (r = -0.54, p < 0.01) with the dialysis duration and directly (r = 0.413, p < 0.05) with the corresponding beta-2-microglobulin determinations. We speculate that reduced antiprotease activity may play a role in amyloidogenesis in the setting of long-term hemodialysis.