The yeast cytoplasmically-inherited nonsense suppressor [PSI+] determinant is presumed to be a manifestation of the aggregated prion-like state of the Sup35 protein. Overexpression of the Sup35 protein induces generation of [PSI+] determinants with various suppressor efficiency and mitotic stabilities. Here, we demonstrate that the relative frequency of appearance of [PSI+] with different properties depends on the SUP35 allele used to induce their generation. The difference in properties of [PSI+] determinants was preserved after their transmission from one yeast strain to another. This difference correlated with variation in properties of the Sup35 protein. A novel type of prion instability was observed: some [PSI+] with weak suppressor efficiency could convert spontaneously into strong suppressor determinants. Copyright © 2001 John Wiley & Sons, Ltd.