Patients with chronic bronchial asthma show a depressed ventilatory response to hypoxia (DVH) but the underlying mechanism remains unclear. We tested whether DVH existed in ovalbumin (Ova)-treated guinea pigs, an established animal model of asthma. Twelve guinea pigs were exposed to Ova (1% in saline) or saline aerosol (control) for 5 minutes, 5 days per week for 2 weeks. After completing aerosol exposure, the animals were anesthetized and exposed to systemic hypoxia. Ova-treatment had no effects on animal body weight, baseline cardiorespiratory variables, or arterial blood O₂ and CO₂ tensions, but attenuated the ventilatory response to hypoxia (10 breaths of pure N₂) by 65% (P < 0.05). When the animals were subjected to intracarotid injections of sodium cyanide (20 µg) and doxapram (2 mg) to selectively stimulate carotid chemoreceptors, the ventilatory responses were reduced by 50% (P < 0.05) and 74% (P < 0.05), respectively. In contrast, Ova-exposure failed to affect the ventilatory response to CO₂ (7% CO₂, 21% O₂, balanced with N₂ for 5 min (P > 0.05). Furthermore, the apneic response evoked by stimulating bronchopulmonary C-fibers (PCFs) with right atrial injection of capsaicin (5 µg) was markedly increased in the Ova-sensitized group (5.02 ± 1.56 s), as compared to the control group (1.82 ± 0.45 s; P < 0.05). These results suggest that Ova-sensitization induces a DVH in guinea pigs, which probably results from an attenuation of the carotid chemoreceptor-mediated ventilatory excitation and an enhancement of the PCFmediated ventilatory inhibition.