This study was undertaken to confirm the presence of alpha-1-antitrypsin (alpha 1-AT) in human brain tumors and to attempt to elucidate its significance. Seventy-seven consecutive unselected patients with various brain tumors were entered in this study. The alpha 1-AT and alpha 2-macroglobulin contents of the tumor extracts were qualitatively assessed by Ouchterlony immunodiffusion techniques. Plasminogen activator (PA) activity was assayed electrophoretically on sodium dodecyl sulfate gels. The patients were were divided into two groups according to the positivity of their tumors to alpha 1-AT. Sixty-eight percent of the tumors were positive for alpha 1-AT, and all specimens were negative for alpha 2-macroglobulin. Clinical and biological parameters obtained in all study patients failed to show statistically significant differences between the two groups with the exception of PA activity (p = 0.001), the peritumoral edema as seen on computerized tomography, and the preoperative serum fibrinogen level. These three parameters were higher in the group with specimens positive to alpha 1-AT. This study supports the hypothesis that alpha 1-AT is produced primarily by tumor cells in proportion to the regional proteolytic and inflammatory activity, and may protect the tumor cells.