The phenotypic effects of a novel X-chromosome linked mutation were studied in the offspring of male mice treated with the mutagen ethyl nitrosourea (ENU). Studies of X-chromosome inactivation patterns in females heterozygous for the mutation (ENU/+) has delineated four distinct cell lineages affected by the mutation, namely, B, pre-B and T lymphoctyes, erythrocytes and skeletal myocytes. The penetrance of the mutation depended on the age of mice, the cell lineage affected by the mutation and the stage of maturation of the cell lineage. Studies of B cells in females heterozygous for the mutation and the X-linked mutation, xid that affects B but not pre-B cells, indicated that the two mutations were not allelic. Factors influencing differences in X-chromosome inactivation between cells and hybrids and their relationship to alleles of the X-chromosome controlling element (Xce) in the ENU-mutant and parental strains were studied. It was not possible to identify the effects of the mutation on the immune system in functional terms either by flow cytometric analysis of leukocytes or after sensitisation to oxazolone. Results imply the mutation renders the affected cell lineages susceptible to competition with normal cells in the heterozygote, rather than there being any fundamental defect in cell function and that the mutation may be in a gene encoding a component of the cell cycle or controlling a maturation step.