TH2 clones may produce very variable amounts of IL-4. Among six TH2 clones prepared from homozygous or heterozygous mice in which Gfp replaced the first exon of Il4, a range of patterns of CpG methylation in the Il4/Il13 locus was observed correlating with the degree of expression of IL-4 or green fluorescence protein. Patterns of histone acetylation also showed differences between "high" and "low" TH2 clones. These results indicate that in TH2 cells the Il4 locus may display variable patterns of chromatin accessibility associated with distinct degrees of IL-4 expression. This finding suggests a regulation of IL-4 expression keyed to the function of this cytokine in cell/cell interactions and in the regulation of threshold responses.