Like MTL-heterozygous (a/␣) cells, white MTL-homozygous (a/a or ␣/␣) cells of Candida albicans, to which a minority of opaque cells of opposite mating type have been added, form thick, robust biofilms. The latter biofilms are uniquely stimulated by the pheromone released by opaque cells and are regulated by the mitogenactivated protein kinase signal transduction pathway. However, white MTL-homozygous cells, to which opaque cells of opposite mating type have not been added, form thinner biofilms. Mutant analyses reveal that these latter biofilms are self-induced. Self-induction of a/a biofilms requires expression of the ␣-receptor gene STE2 and the ␣-pheromone gene MF␣, and self-induction of ␣/␣ biofilms requires expression of the a-receptor gene STE3 and the a-pheromone gene MFa. In both cases, deletion of WOR1, the master switch gene, blocks cells in the white phenotype and biofilm formation, indicating that self-induction depends upon low frequency switching from the white to opaque phenotype. These results suggest a self-induction scenario in which minority opaque a/a cells formed by switching secrete, in a mating-type-nonspecific fashion, ␣-pheromone, which stimulates biofilm formation through activation of the ␣-pheromone receptor of majority white a/a cells. A similar scenario is suggested for a white ␣/␣ cell population, in which minority opaque ␣/␣ cells secrete a-pheromone. This represents a paracrine system in which one cell type (opaque) signals a second highly related cell type (white) to undergo a complex response, in this case the formation of a unisexual white cell biofilm.Approximately 90% of Candida albicans isolates are a/␣ and 10% either a/a or ␣/␣ (24, 25, 50). For a/␣ strains to mate, they must undergo homozygosis to a/a or ␣/␣ (20, 21, 29). Then, a/a and ␣/␣ strains must switch from the white to opaque phenotype (46) in order to be mating competent (27,30). Opaque cells secrete a cell type-specific pheromone, which stimulates the mating response in cells of opposite mating type (5,26,38). However, in a fashion unique to C. albicans, these pheromones also induce mating-incompetent white cells, but not matingcompetent opaque cells, of opposite mating type to form robust biofilms, similar morphologically to those formed by a/␣ cells (13, 42-44, 48, 53-55). These MTL-homozygous white cell biofilms have been demonstrated in vitro to facilitate mating between opaque a/a and ␣/␣ cells (13,48).Although the addition of minority opaque cells of opposite mating type (1 to 10%) to a population of white cells increases the thickness of the final white cell biofilm by more than 50%, single-sex white a/a or ␣/␣ cell populations, to which cells of opposite mating types have not been added, also form robust biofilms composed of a basal layer of yeast cells and a thick upper layer of hyphae and matrix (13,(42)(43)(44)(53)(54)(55). We previously showed that deletion of the ␣-receptor gene STE2 results in highly reduced, abnormal white a/a cell biofilms in the absence of minority opaque ␣/␣ cells, suggesting t...