Interleukin (IL)-1 is a potent proinflammatory cytokine that is markedly overexpressed in the brains of patients with Alzheimer's disease (AD). The IL-1A [-889] allele 2 has been shown to increase AD risk, probably by upregulating the inflammatory cascade in the disease process. A case-control study utilizing a clinically well-defined group of 298 sporadic AD patients and 306 control subjects was performed to test this association. Our data show that the IL-1A allele 2 is a risk factor in a dose-dependent manner, the risk of developing AD with two copies of the IL-1A allele 2 (odds ratio 3.1, 95 % CI 1.30-7.45) being approximately double that of one copy of the IL-1A allele 2 (odds ratio 1.4, 95 % CI 0.99-1.94, P for trend = 0.0004). Furthermore, the risk associated with the IL-1A allele 2 was not restricted to AD patients of a particular age, and we could confirm this association in our early-onset and late-onset AD patients.