Candida albicans strains with a deletion of the mitogen-activated protein kinase tyrosine phosphatase gene (CPP1) are derepressed in the yeast-to-hyphal transition on solid surfaces in vitro at ambient temperatures and this gene is therefore required for repression of the yeast-to-hyphal switch. The pathology caused by a CPP1 null mutant strain was compared with that of the null mutant into which the wild-type CPP1 gene was introduced by homologous recombination and with the wild-type parent strain in a murine mycotic mastitis model. The mammary glands of lactating mice (at day 5 postpartum) were infected for 2, 4 and 6 days with 1 × 105, 1 × 106 and 1 × 107 cell-forming units before euthanasia. Infected and non-infected control glands were evaluated histopathologically. The null mutant strains showed less severe pathology than the two control strains. The Cpp1p tyrosine phosphatase may thus be considered a virulence determinant during localized infection in C. albicans.