Yeast genomes contain variable number tandem repeats (VNTRs) within coding regions of DNA. A significant number of these genes are involved in cell rescue, defence and virulence and are regulated by genetic elements associated with stress. Alleles that encode variable length, single amino acid tracts, are mainly associated with transcription and proteins localized within the nucleus. Alleles that encode proteins containing oligopeptide repeats or minisatellites are over-represented in cell wall and extracellular space locations. Functional analysis of the latter group reveals that these proteins are involved in biogenesis of cellular components and in interaction with the cellular environment, especially in relation to stress resistance, heat shock response, temperature perception and adhesion. A significantly high number of these proteins have regions rich in threonine and/or serine that contain repeated sequences, variable in length within yeast species. DNA sequences encoding serine- and/or threonine-rich regions give rise to polymorphic alleles and therefore may confer a selective advantage to cells. We propose that these regions are the focus of mutational and recombination events that, when coupled with directed selection, may contribute to genetic variation within stress-related genes.