The pulmonary neuroendocrine system includes pulmonary neuroendocrine cells (PNECs) and neuroepithelial bodies (NEBs) that are distributed throughout respiratory epithelium and regulate lung growth and maturation antenatally. Abnormalities in this system have been linked to many hypoxia-associated pediatric pulmonary disorders. Hemoglobin (Hb) Bart disease is a severe form of α-thalassemia resulting in marked intrauterine hypoxia with hydrops fetalis (HF) and usually death in utero. Affected fetuses can serve as a naturally occurring human model for the effects of intrauterine hypoxia, and we postulated that these effects should include changes in the pulmonary neuroendocrine system. Bombesin immunostaining was used to assess PNECs and NEBs in stillborn fetuses with Hb Bart HF ( n = 16) and with HF from other causes ( n = 14) in comparison to non-HF controls. Hb Bart HF showed a significant increase in the proportion of PNECs in respiratory epithelium ( P = .002), mean number of NEB nuclei ( P = .03), and mean size of NEBs ( P = .002), compared to normal non-HF controls. Significant differences were not observed between HF due to other causes and non-HF controls with normal lungs. Non-HF controls with pulmonary hypoplasia showed significant increases in PNECs compared to HF cases not due to Hb Bart HF, implying HF alone does not cause such increases. In contrast, no significant differences were noted between non-HF controls with pulmonary hypoplasia and Hb Bart cases. Hb Bart HF may provide a useful model for studying the pulmonary neuroendocrine system under chronic intrauterine hypoxia.