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Background: Abnormal activity of two enzymes relevant to neurodevelopment, namely nuclear-distribution element-like 1 (Ndel1) and angiotensin I-converting enzyme (ACE), was reported in individuals with schizophrenia; to our knowledge, these oligopeptidases were never measured in bipolar disorder (BD)., Aims: Evaluate the enzyme activity of Ndel1 and ACE in euthymic individuals with BD type 1 which was compare to healthy control (HC) group., Methods: Ndel1 and ACE activities were assessed in the serum of individuals with BD type 1 according to DSM-IV criteria (n = 70) and a HC group (n = 34). The possible differences between BD type 1 and HC groups were evaluated using Analysis of Covariance (ANCOVA), and the results were adjusted for age, gender and body mass index., Results: We observed a positive correlation between Ndel1 activity and the total YMRS score in BD group (p = 0.030) and a positive correlation between ACE activity and Ham-D score (p = 0.047). ANCOVA analysis showed lower Ndel1 activity in BDs compared to HCs. Interestingly, we did not observe between-groups differences in ACE activity, despite the recognized correlation of ACE activity levels with cognitive functions, also described to be worsened in psychiatric patients., Conclusion: Oligopeptidases, especially Ndel1, which has been strongly correlated with neurodevelopment and brain formation, are potentially a good new target in the study of the neurobiology of BD., Limitations: The relatively small sample size did not permit to examine the cause-effect relationship of clinical dimensions of BD and the enzymatic activity., (Copyright © 2018. Published by Elsevier B.V.)