We have identified the YPD1 phosphohistidine intermediate two-component gene of Candida albicans. YPD1 has an open reading frame of 552 bp. It is located on chromosome 1 and an mRNA specific for YPD1 is detected under both yeast and hyphal growth. YPD1 encodes a protein of 184 amino acids with an estimated molecular mass of 20.5 kDa. A search for similarities with other proteins in databases showed that CaYpd1p exhibits the greatest overall similarity with Ypd1p from Saccharomyces cerevisiae (34.2% identity; 49.4% similarity) as well as with the C-terminus half of a protein from Schizosaccharomyces pombe (Accession No. CAA22174). However, CaYpd1p also shows similarity with other eukaryotic and prokaryotic proteins which function as phosphohistidine intermediates in two-component phospho-relay systems. In these cases, similarity was restricted to the amino acid sequences which surround the conserved histidine residue that is phosphorylated. In addition, CaYPD1 (but not CaYPD1(H69Q)) complements the lack of YPD1 in S. cerevisiae. This observation supports the premise that CaYpd1p also may function as a phosphohistidine intermediate protein in C. albicans.