ABSTRACT Uniparental inheritance (UPI) of mitochondria is common among eukaryotes. The underlying molecular basis by which the sexes of the parents control this non-Mendelian pattern of inheritance is yet to be fully understood. Two major factors have complicated the understanding of the role of sex-specific genes in the UPI phenomenon: in many cases (i) fusion occurs between cells of unequal size or (ii) mating requires a large region of the genome or chromosome that includes genes unrelated to sex determination. The fungus Phycomyces blakesleeanus is a member of the Mucoromycotina and has a simple mating type locus encoding only one high-mobility group (HMG) domain protein, and mating occurs by fusion of isogamous cells, thus providing a model system without the limitations mentioned above. Analysis of more than 250 progeny from a series of genetic crosses between wild-type strains of Phycomyces revealed a correlation between the individual genes in the mating type locus and UPI of mitochondria. Inheritance is from the plus (+) sex type and is associated with degradation of the mtDNA from the minus (−) parent. These findings suggest that UPI can be directly controlled by genes that determine sex identity, independent of cell size or the complexity of the genetic composition of a sex chromosome.