Spontaneously arising erythromycin-resistant mutants were isolated in the "petite-negative" yeast Kluyveromyces lactis. Two independently arising mutants were studied, in one erythromycin-resistance was conferred by a single dominant nuclear gene, and in the other the resistance was extrachromosomally inherited. In fermentable medium growth of sensitive and resistant strains in presence or absence of erythromycin does not qualitatively change the cytochrome absorption spectra, whereas oxygen uptake of parental strains growing in glucose-medium is affected by the drug. The importance of "petite-negative" yeasts like Kluyveromyces lactis for the study of nucleo-cytoplasmic interrelations is discussed.