A C-to-A base substitution has been identified at bp -571 in the IL-10 promoter and has been linked to numerous diseases. To investigate the role of this polymorphism on IL-10 production, T cells, B cells and monocytes were enriched from peripheral blood from subjects either homozygous for the C or A allele. Treatment of monocytes and B cells with lipopolysaccharide from individuals homozygous for the C allele resulted in higher levels of IL-10 production as compared to monocytes from individuals homozygous for the A allele. Though not statistically significant, when B cells were treated with anti-IgM or T cells with concanavalin A higher levels of IL-10 were produced from individuals homozygous for the A allele. Changes in IL-10 protein production were paralleled by similar changes in IL-10 mRNA production. These results demonstrate that changes in IL-10 production observed due to the -571 genotype depend on both cell type and stimulus.