Infection with Cryptococcus species is often considered an AIDS-defining illness, the outbreak of Cryptococcus gattii on Vancouver Island underscores the broad potential of the Cryptococcus neoformans species complex to evade host immune defenses and cause disease. There are several simple developments that need to be made to maximize the use of C. neoformans genomes. One development is the publication of the genomes of the serotype A and C. gattii strains and a finalized nomenclature for each gene in each strain sequenced, preferably as similar to other designations as possible. Examples of larger-scale screens include a series on melanin, morphology, suppressor screens of light sensitivity of mating , and growth under hypoxic conditions. In the first, "alternative" hosts have been used, with the most success obtained thus far in the nematode Caenorhabditis elegans. Importantly, both genes were found to be required for maximal virulence in murine inhalation models. Protein-protein interactions are important in a number of regulatory events involved in cryptococcal virulence and have been detected in C. neoformans by using a variety of methods. Single gene interactions have been detected by coimmunoprecipitation studies of the nuclear heat shock transcription factor, Hsf1, with a coactivating heat shock homolog, Ssa1, during laccase induction. A major experimental advantage of C. neoformans, uncommon among the human pathogenic fungi, is the established complete sexual cycle that enables classical Mendelian crosses and genetics.