Protein tyrosine phosphatase ζ (PTPζ/RPTPβ) is a receptor-like protein tyrosine phosphatase specifically expressed in the brain. Alternative splicing produces three isoforms of this molecule: PTPζ-A, the full-length form of PTPζ; PTPζ-B, the short form of PTPζ; and PTPζS, an extracellular variant. Here, we identified all these isoforms, including PTPζ-B, as chondroitin sulfate proteoglycans, and characterized their carbohydrate modification and expression profiles in the rat brain. The level of PTPζ-A expression was maintained during the prenatal period and decreased rapidly after birth. PTPζ-S was expressed in a similar manner, although the postnatal decrease was gradual. In contrast, relatively constant amounts of PTPζ-B were observed from embryonic day 13 (E13) through adulthood. PTPζ-A and -S were constantly expressed only as proteoglycans during development, but a substantial amount of PTPζ-B was detected in a non-proteoglycan form at E13–15. Moreover, PTPζ-B did not contain Lex, HNK-1 carbohydrate, or keratan sulfate, although PTPζ-A and -S were generally modified with these carbohydrates. L cells transfected with PTPζ-A and -B cDNAs expressed these proteins as enzymatically active chondroitin sulfate proteoglycans. The PTPζ-A and -B in L cells showed essentially similar localizations in cell cortical structures on immunofluorescence microscopy, although immature or processed forms of PTPζ-A were accumulated additively in intracellular patchy structures. These results show that the three isoforms of PTPζ are differentially regulated during development, and that the extracellular deleted region in PTPζ-B is important for determination of carbohydrate modification.