The leaky expression of the yeast mitochondrial gene oxi1, containing a framshift mutation (+1), is caused by natural frameshift suppression, as shown previously (Fox and Weiss-Brummer 1980). A drastic decrease in the natural level of frameshifting is found in the presence of the parr-454 mutation, localized at the 3' end of the 15 S rRNA gene. This mutation causes resistance to the antibiotic paromomycin in the yeast strains D273-10B and KL14-4A (Li et al. 1982; Tabak et al. 1982). The results of this study imply that in the yeast strain 777-3A this mutation alone is sufficient for restriction of the level of natural frameshifting but is insufficient to confer resistance to paromomycin. A second mutation, arising spontaneously with a frequency of 10(-4) leads, in combination with the parr-454 mutation, to full paromomycin resistance in strain 777-3A.