In this study, we have assessed any change in the frequency of the GG homozygotes of the 174 IL-6 polymorphism with increasing age, arguing that if IL-6 tracks with functional disability and age-related diseases, then there may be attrition or reduction in the frequency of homozgyous subjects, who produce higher levels of IL-6 in serum, in older survivors in a population. We have tested this hypothesis in a large group of free-living, mentally competent, nonagenarian and octogenarian subjects from the Belfast Elderly Longitudinal Ageing Study-BELFAST study and found that the frequency of GG homozygotes with IL-6-174C/G polymorphism decreases with age by about 10%, compared with young controls. In addition we find that CC homozygotes have higher serum levels of IL-6 levels compared with GG (P=0.055), with reciprocal and significant changes in the anti-inflammatory IL-10 (P=0.05). Both IL-6 and IL-10 were spontaneously produced from separated mononuclear cell monolayers in elderly subjects, with significantly higher levels of secreted IL-10 supernatant levels (P=0.05) at 20 h, for G allele subjects carrying the IL-6-174C/G polymorphism. In conclusion, in the BELFAST study, there appears to be a reduction in the frequency of GG homozygotes in the octo/nonagenarian age group and a higher serum IL-6 level associated with CC homozygotes with reciprocal changes for the anti-inflammatory cytokine IL-10.