Little is known about the number of mouse protein tyrosine phosphatases (PTPs) and their developmental and tissue-specific expression patterns. A new procedure based on fingerprinting of amplified catalytic domains detects expression of at least 20 different mouse PTPs during development. The majority of these PTPs show developmentally regulated expression patterns; some display a unique tissue specificity. Diagnostic fragments detected in the fingerprint analysis are used here as specific probes to directly clone two previously unknown ubiquitously expressed PTPs and PTP1C, a protein tyrosine phosphatase highly expressed in thymus RNA. The fingerprinting procedure is also applicable to the analysis of protein tyrosine kinases and may also be used to study the expression pattern of other multigene families.