CD45 is a protein tyrosine phosphatase implicated in T and B cell activation, differentiation, and development. It dephosphorylates specific tyrosine residues on its substrates, principally on the Src-family of protein tyrosine kinases, thus regulating T cell or B cell activation during the immune response. In this study, we present the partial CD45 nucleotide and deduced amino-acid sequences for the owl monkey (Aotus vociferens). There is 97% identity in the nucleotide sequence and 96% in the amino acid sequence with the human counterpart. Aotus CD45 undergoes alternative splicing on the extracelular N-terminal tail, and has several conserved features characteristic of other species. This includes the two Tyr phosphatase domains and some residues and/or motifs involved in docking of signaling molecules, intramolecular interactions, and CD45 activity and activity regulation (YINAS, GXGXXG, WPD, and YWP motifs, and the Cys residues). This suggests that the Aotus CD45 molecule is a functional enzyme and that initial lymphocyte activation in Aotus monkeys and humans is very similar. Together with previous reports from our laboratory, this work supports the contention that immune responses in Aotus are similar to those of humans, and supports the strategy for using this experimental model for studies on activation of T lymphocytes in response to specific antigens. Am. J. Primatol. 57:1–11, 2002. © 2002 Wiley-Liss, Inc.