To understand the molecular mechanisms that control the reversible morphologic transition from mycelia to yeast in dimorphic fungi, we have isolated and characterized a cdc2 gene from Histoplasma capsulatum. This organism is a dimorphic pathogenic fungus that grows as a filamentous saprobic mold in soil and as a unicellular pathogenic yeast in human tissue. The cloned gene, whose protein product has a high degree of homology with other members of the cdc2 family, is split into four exons and three introns of 95, 52 and 85 nucleotides. Analyses of cDNA clones confirm the presence of the eukaryotic splice donor (GT) and acceptor (AG) sites. The spliced gene codes for a protein of 324 amino acids (aa) with a predicted molecular mass of 36.9 kDa. The H. capsulatum cdc2 product has 71% aa identity with Saccharomyces cerevisiae and 70% with Schizosaccharomyces pombe. The deduced protein contains the sequence, PSTAIRE, that is normally found in most p34cdc2 proteins. H. capsulatum cdc2 is transcriptionally regulated during the morphologic mycelium<==>yeast transitions and is more actively transcribed in the yeast than in the mycelial phase.