Abstract Aim: Ghrelin has been implicated as a modulator of numerous physiological pathways. To date, there have not been any studies describing the role of ghrelin in modulating the chemoreflex control of pulmonary ventilation. Yet the respiratory system impacts, at least to some degree, on virtually all homeostatic control systems. Chronic hypoxia (CH) can cause fundamental changes in ventilatory control, evident by alterations in the acute hypoxia ventilatory response (HVR). As ghrelin plays an important role in metabolic homeostasis, which is tightly linked to ventilatory control, we hypothesized that ghrelin may modulate HVR, especially following CH. Methods: Whole body plethysmography was used to measure the HVR (8 O(2) for 10 min) in male Sprague-Dawley rats (body wt approximately 180-220 g) before and after 14 days of CH (CH = 10 O(2)). During CH, rats received daily subcutaneous injections of either saline (control; n = 5) or ghrelin (150 mug kg(-1) day(-1); n = 5). The HVR was measured in another four rats that had received daily injections of ghrelin during normoxia for 7 days. Results: Ghrelin did not significantly alter basal ventilatory drive or acute HVR in normoxic rats. However, the acute HVR was accentuated following CH in ghrelin-treated rats compared with saline-treated rats. Conclusions: These results describe the impact that ghrelin has in altering ventilatory control following CH and, although the mechanisms remain to be fully elucidated, provide guidance for future ghrelin-based studies interpreting physiological data indirectly related to the chemoreflex control of pulmonary ventilation.