Protein tyrosine phosphatases are important components of signal transduction pathways. The authors have used reverse transcription/polymerase chain reactions to accomplish a comprehensive examination of the RNA expression for 58 distinct mammalian protein tyrosine and dual specificity phosphatase (PTPase) and PTPase-like genes in the normal human diploid fibroblast cell line WI-38. Thirty-seven of these PTPase genes express easily measurable RNA, and four simultaneously express the RNA for two or more isoforms. Messages for an additional eight PTPase genes are detectable at low levels. Only 14 known PTPase genes do not express measurable RNA under our conditions. For purposes of comparison, the authors also assessed the PTPases expressed in the WI-38 cell line using highly degenerate primers to conserved motifs found in the classical tyrosine-specific PTPases. Only eight of the 22 classic tyrosine-specific PTPases detected using the specific primers were detected using these degenerate primers. Our panel of specific PTPase primers should be very useful for semiquantitatively assessing the repertoire of PTPases expressed by cells.