Alpha-1-antitrypsin (alpha1-antitrypsin) is a major protease inhibitor controlling tissue degradation. Reduced alpha1-antitrypsin levels could result in a change of collagen metabolism. Previous studies have described decreased alpha1-antitrypsin levels in patients with Peyronie's disease. However, only a small number of patients were analyzed, and the reason for the decreased alpha1-antitrypsin levels remained unclear. This study investigated prospectively the levels of alpha1-antitrypsin in patients with Peyronie's disease, as well as genetic variation in the coding region of the alpha1-antitrypsin gene.Alpha1-antitrypsin levels were determined prospectively in 94 patients with Peyronie's disease and compared to healthy controls. Analysis of the alpha1-antitrypsin gene (S, Z variants; single nucleotid polymorphisms [SNPs]: T-395A, M2, M3, G6118A) was done in 141 Peyronie's patients including 43 patients with investigated alpha1-antitrypsin serum levels and compared to healthy controls.In patients with Peyronie's disease, the alpha1-antitrypsin levels seemed to be decreased significantly compared to healthy controls. However, in the age matched approach no significant differences occurred. Moreover, a significant (p < 0.002) decrease of the alpha1-antitrypsin level with increasing age was observed, explaining the initial differences between the two groups. In confirmation with these findings, no significant association of the alpha1-antitrypsin gene variants with Peyronie's disease was detectable.The results of this study do not indicate a significant association between Peyronie's disease and decreased alpha1-antitrypsin levels. Low alpha1-antitrypsin levels in Peyronie's patients are, rather, an age-related phenomenon, as revealed by the comparison with aged matched healthy controls. The decrease of the alpha1-antitrypsin serum level with increasing age has not been described before.