IL-6 in vitro production, as well as the serum/plasma concentration of the cytokine, increase with age. In the present investigation, a total of 62 individuals (31 males and 31 females), aged from 29 to 93 years of age (mean age of males: 60.4 years; mean age of females: 59.4 years) were assessed for IL-6 plasma concentration, and for IL-6 in vitro production, using supernatants of 4h cultured adherent peripheral blood mononuclear cells (aPBMC). The subjects were examined for a C to G transition at nucleotide -174 of the IL-6 gene promoter (-174 C/G locus), and were classified as C allele carriers (C+) or non-carriers (C-). We found that: (i) aPBMC from C+ individuals produced smaller amounts of IL-6 in vitro than C- individuals; (ii) IL-6 production by aPBMC increased with age in C+ but not in C- subjects; (iii) there was no correlation between IL-6 plasma levels and in vitro IL-6 production by aPBMC; (iv) IL-6 C+ individuals had lower plasma levels than C- individuals, and this phenomenon was significant only in men. On the whole our data indicate that the production of IL-6 is genetically controlled and age- and gender-dependent.