Chronic local inflammatory reaction involving reactive microglia is one of the major pathological events in Alzheimer's disease (AD). There is growing evidence that the chemokine receptor CCR5 is up-regulated in AD brain and plays a role in the recruitment and accumulation of microglia in senile plaques. A 32-base pair deletion in the CCR5 gene (CCR5-Delta32 mutant allele) confers resistance to HIV-1 infection by preventing expression of the receptor on the cell surface. Several other reports have shown a similar protective effect of CCR5-Delta32 mutation towards certain chronic inflammatory diseases. Given the potential importance of CCR5 in brain inflammation, we hypothesized that individuals carrying the CCR5-Delta32 allele would show a reduced risk of AD. So, we performed a case-control study in 376 Spanish AD patients and 369 healthy controls. The frequency of the CCR5-Delta32 allele in our AD sample was 7.8%, not significantly different from our control sample group (5.8%). The present study indicates that the CCR5-Delta32 allele is not a preventive factor for AD.