Changes in DNA methylation are often associated with the modulation of gene expression. The DNA methylation patterns of six genes whose expression is regulated with terminal myeloid maturation were examined in HL-60 cells before and after their differentiation towards granulocytes. Methylation patterns were stable in five of these genes even with strong up- or down-regulation of mRNA levels. A somatic hybrid cell formed from HL-60 and B-lymphoid cells was studied for mRNA expression and DNA methylation of several of these genes. The pattern of methylation of the genes studied in the hybrid cells was a chimera of the parental patterns. These data suggest that changes in DNA methylation may not be necessary for the modulation of expression of many genes during terminal myeloid differentiation. Furthermore, somatic hybrid cell experiments suggest that specific DNA methylation patterns from both parental cells are inherited in a chimeric pattern by the hybrid and are independent of gene expression.