Developmental and trauma-induced mechanism(s) that modify inflammation and immune responses in blood cells were recently found to be regulated by acetylcholine. Here, we report corresponding blood cell-specific changes in acetylcholinesterase splice variants. Plasmon resonance and flow cytometry using acetylcholinesterase variant-specific antibody probes, revealed a progressive increase in myeloid cell fractions expressing the apoptosis-related acetylcholinesterase-S variant from newborns to adult controls and post-delivery mothers. Hematopoietic cell fractions positive for the myeloproliferative acetylcholinesterase-R variant, were similarly high in post-partum blood, both intracellular and on the cell surface. Moreover, intracellular acetylcholinesterase-S protein amounts as reflected by fluorescence intensity measurements remained unchanged in myeloid cells from post-partum mothers as compared with matched controls. Unlike brain neurons, which over-express intracellular acetylcholinesterase-R under stress, lymphocytes from post-partum mothers presented increased surface acetylcholinesterase-S and pronounced decreases in both the expression and contents of surface acetylcholinesterase-R. Peripheral stimuli-induced modulations in acetylcholine regulation may hence reflect blood cell lineage-dependent acetylcholinesterase splice variations.