Acute hyperosmolality in the Pekin duck results in an extracellular acidosis and hypercarbia without any stimulation of ventilation. The development of the extracellular acidosis is accompanied by the concurrent development of an intracellular alkalosis systemically which has been hypothesized to depress ventilation (Kasserra et al., J. Appl. Physiol., 1993). In order to investigate this apparent suppression of ventilation, the ventilatory response to various respiratory challenges (CO2, O2, K+) was studied both before (normosmotic) and after (hyperosmotic) hypertonic sucrose infusion. Increased plasma osmolality caused a significant drop in arterial pH of 0.06 +/- 0.01 units and a 4 Torr increase in PaCO2, yet did not stimulate any significant increase in ventilation despite a significant increase in oxygen consumption. Acute hyperosmolality increased the PaCO2 associated with resting ventilation, and decreased the magnitude of the ventilatory response to a given increase in PaCO2, compared with the response to the same ventilatory challenge in normosmotic animals. Acute hyperosmolality increased the ventilatory response to hypoxia and K+ compared with normosmotic animals. The opposite effect of hyperosmolality on the ventilatory responses to hypercapnia compared with hypoxia suggests that the mechanisms of chemoreception for hypercapnia and hypoxia are different. The depressed ventilatory response curve to increased PaCO2 and decreased arterial pH during hyperosmolality, both alone and during the hypercapnic challenge, suggests that the peripheral chemoreceptor response to pH and CO2 is suppressed. It is hypothesized that the suppression results from the intracellular alkalosis occurring during acute hyperosmolality.