Phenotypic switching in Wangiella dermatitidis between polarized growth processes leading to yeast budding or hyphal apical extension and nonpolarized processes leading to isotropically enlarged forms that may become multicellular is a cell-cycle related phenomenon. Exit of yeasts from the budding growth cycle by this polymorphic agent of phaeohyphomycosis can be induced by incubation of wild-type (wt) cells in pH 2.5 medium at 25 degrees C, or of certain temperature-sensitive, cell-division-cycle (cdc) mutants at pH 6.5 at 37 degrees C. Continued incubation under these semirestrictive conditions causes yeasts to form unbudded, multinucleate, multicellular phenotypes that resemble the sclerotic bodies of chromoblastomycotic fungi. However, new results with Ca2+ indicate that at pH 2.5 critical, but low, concentrations of this ion are crucial for regulating multicellular form development, higher concentrations allow maintenance of polarized growth, and that switching between polarized and nonpolarized growth may involve a Ca2+/proton exchange mechanism. Support for this important role for Ca2+ is provided by experiments with EGTA in media buffered against pH change at near neutrality. Under these conditions, withholding Ca2+ with high EGTA concentrations caused yeasts to arrest in a terminal phenotype characterized by the presence of a bud initial that tended not to enlarge. In contrast, lower concentrations of EGTA often induced yeast-to-multicellular-form conversion. Other new results have suggested that even brief culture of yeasts under conditions that arrest their budding growth cycles may induce commitment to phenotypic transitions.(ABSTRACT TRUNCATED AT 250 WORDS)