Data supporting the hypothesis that dopamine-2 receptors (D-2-R) contribute to time-dependent changes in the hypoxic ventilatory response (HVR) during acclimatization to hypoxia are briefly reviewed. Previous experiments with transgenic animals (D-2-R 'knockout' mice) support this hypothesis (J. Appl. Physiol. 89 (2000) 1142). However, those experiments could not determine (1) if D-2-R in the carotid body, the CNS, or both were involved, or (2) if D-2-R were necessary during the acclimatization to hypoxia versus some time prior to chronic hypoxia, e.g. during a critical period of development. Additional experiments on C57BL/6J mice support the idea that D-2-R are critical during the period of exposure to hypoxia for normal ventilatory acclimatization. D-2-R in carotid body chemoreceptors predominate under control conditions to inhibit normoxic ventilation, but excitatory effects of D-2-R, presumably in the CNS, predominate after acclimatization to hypoxia. The inhibitory effects of D-2-R in the carotid body are reset to operate primarily under hypoxic conditions in acclimatized rats, thereby optimizing O-2-sensitivity. (C) 2003 Elsevier Science B.V. All rights reserved.