Maternally transmitted antigen (Mta) is a murine cell-surface molecule defined by the reactivity of specific H-2 nonrestricted cytotoxic T lymphocytes (CTL-s)1,2. Maternal transmission appears to be under control of a stable genetic factor in the cytoplasm of the ovum3,4. In view of the known maternal inheritance of mitochondria5-7, we have assessed their involvement in Mta expression using the mitochondria specific poison Rhodamine 6G (R6G)8,9. We report here that Mta expression in somatic cell hybrids requires functional mitochondria from the Mta+ parent cell line. Mta expression was dominant in hybrids from the fusion of Mta + and Mta- cells. However, pretreatment of the Mta + parent with R6G resulted in hybrids which were Mta-, or diminished in Mta expression. These data strongly implicate mitochondrial DNA (mtDNA) in the expression of a cell-surface molecule, and define a system for studying a previously unrecognized mitochondrial function. To our knowledge, this is the first evidence for mitochondrial control of the expression of a cell membrane molecule in eukaryotes. © 1983 Nature Publishing Group.