Taking advantage of the high frequency of conjugation tube formation in mating mixtures and alpha-pheromone-treated a/a cells derived from saturation phase cultures of opaque cells of Candida albicans, 56 up-regulated and 30 down-regulated genes were identified employing microarray and Northern analyses. Combining these results with previous profiling studies of pheromone-induced cells, a more comprehensive transcript profile was developed for comparison with Saccharomyces cerevisiae. This comparison revealed the following: (i) that while a majority of mating-associated genes are regulated similarly between the two species, a significant minority are regulated dissimilarly; (ii) that filamentation genes are uniquely up-regulated and opaque-specific genes uniquely down-regulated during C. albicans mating; and (iii) that a newly identified class of genes is selectively down-regulated in opaque, but not white, cells that have entered saturation phase in a growth culture and then are up-regulated by pheromone. The observations that opaque cells are uniquely mating competent, that saturation phase facilitates mating, and that a newly identified group of genes is down-regulated only in opaque cells that have entered saturation phase led us to hypothesize that entering saturation phase may be requisite for mating. A test of this hypothesis revealed, however, that cells, whether in the exponential or saturation phase, may simply have to be in G(1) of the cell cycle to respond to pheromone and that the response includes G(1) arrest. These results add to the lists of similarities and dissimilarities between the mating processes of C. albicans and S. cerevisiae and underscore the unique regulation of filamentation and switching genes in the C. albicans mating process.