The mechanism of preferential transmission (i.e., maternal inheritance) of cytoplasmic genes was investigated with chloroplast DNA of Chlamydomonas as a model system. The behavior of nuclear and chloroplast DNAs were compared in the sexual cycle; DNAs from male and female parents were distinguished by labeling with 14N- or 15NH4Cl and then by making the crosses: 14N (female) × 15N (male) and the reciprocal. Chloroplast DNAs from the two parents followed different paths in the zygote, but nuclear DNAs showed no differences. Chloroplast DNA from the female parent persists in the zygote, but undergoes a density shift of 0.003-0.005 g/cm3 to a lighter buoyant density, whereas that from the male disappears soon after zygote formation. The possibility is discussed that a modification-restriction system may be involved.