IL-1 activity is increased in hemodialysis patients and interest has recently been focused on IL-1 antagonism in various clinical settings. We studied the presence of anti-IL-1 alpha autoantibodies in sera from 49 hemodialysis patients, 159 kidney graft recipients and 89 chronic renal failure patients without renal replacement therapy. Within the three month study period 32.6% of the hemodialysis patients were found to present with anti-IL-1 alpha autoantibodies, in contrast to 5.6% of kidney graft recipients, 8.9% of chronic renal failure patients, and only 1.4% of healthy subjects. The presence of these autoantibodies was neither associated with primary kidney disease nor with the type of dialysis membrane we used. In addition, in antibody positive patients a pronounced increase of IL-1 alpha serum levels within a dialysis session from 14.8 +/- 4.7 pg/ml to 26.4 +/- 11.2 pg/ml (P less than 0.0005) was observed, contrasting to the more even increase from 14.1 +/- 3.1 pg/ml to 19.3 +/- 12.7 pg/ml (P less than 0.05) in the antibody negative group. Neither clinical symptoms due to adverse effects of IL-1 alpha nor some influence on erythropoiesis mediated by IL-1 alpha could be envisaged. Thus, we believe, that anti-IL-1 alpha autoantibodies, present in high frequency in hemodialysis patients, have a neutralizing effect on IL-1 alpha in these patients.