Protein tyrosine phosphatase- (PTP-) is a member of the mammalian LAR family of phosphatases, which is characterized by a cell adhesion-like ectodomain, a single transmembrane segment, and two tandemly repeated intracellular catalytic domains. The expression of PTP- is developmentally regulated in epithelial, neuronal, and neuroendocrine tissues. We previously showed that PTP- is strongly expressed within the fetal, but not adult, rat lung and is localized to the Clara cells and type II pneumocytes. In view of the developmentally regulated pulmonary expression of PTP-, we performed a detailed histological and ultrastructural study of the lungs of PTP- knockout mice we have generated. Our findings indicate no apparent structural abnormalities in the lungs of PTP-^/ mice, including airway and alveolar epithelium. In addition, pulmonary neuroendocrine cells also appear normal, in contrast to pituitary, pancreatic, and gastrointestinal endocrine cells, in the knockout mice, suggesting different developmental regulation of these neuroendocrine cells. These observations suggest compensation for the absence of PTP- during development by related family member phosphatases, such as LAR.