Of four strains of Mycoplasma pneumoniae, highly resistant to erythromycin and related antibiotics, three were homogeneously resistant, but the fourth showed heterogeneous resistance, with only 1% of the cells manifesting this property. Stable, homogeneous resistance was generated in this strain in the presence of erythromycin, whereas the heterogeneous resistance was lost spontaneously on passage in the absence of antibiotics, or on treatment with acridine orange. The mechanism of induction of stable resistance appears to be different from that seen in Staphylococcus aureus.