An assay method is described for determining the frequency of human erythrocytes having a gene expression loss phenotype at the glycophorin A locus presumably due to in vivo somatic mutational events in erythroid precursor cells. Monoclonal antibodies specific for the M and N glycophorin A alleles are used to identify variant cells that lack the expression of one allele in blood samples from MN heterozygotes. Flow cytometry and sorting are used to enumerate and purify variant cells. Using three different antibody combinations which are sensitive to the loss of either the M or the N allele, we find that variant cells occur at a frequency of 1 X 10(-5) in normal donors. We also detect variant cells with an apparent homozygous phenotype suggesting that events leading to homozygosity may occur at similar frequencies to gene loss events. Significant increases in variant cell frequency are observed in cancer patients after exposure to mutagenic chemotherapy drugs.