Both exercise and hypoxia increase pulmonary ventilation. However, the combined effects of the two stimuli are more than additive, such that exercise may be considered to potentiate the acute ventilatory response to hypoxia (AHVR), and vice versa. Exposure to sustained hypoxia of 8 h duration or more has been shown to increase the acute chemoreflex responses to hypoxia and hypercapnia. The purpose of this study was to determine whether sustained exposure to hypoxia also changed the stimulus interaction between the effects of exercise and hypoxia on ventilation. Ten subjects undertook two main protocols on two separate days. On one day, subjects were exposed to isocapnic hypoxia (IH) at an end-tidal partial pressure of O(2) of 55 mmHg and on the other day, subjects were exposed to air as a control (C). Before and after each exposure, the sensitivity of AHVR was assessed during both resting conditions and exercise at 35% of the subjects' maximal oxygen uptake capacity. Average values (means +/- s.d.) obtained for the sensitivity of AHVR from protocol IH were 0.85 +/- 0.35 (rest, prehypoxic exposure), 1.60 +/- 0.66 (exercise, prehypoxic exposure), 1.69 +/- 0.63 (rest, posthypoxic exposure) and 1.81 +/- 0.86 l min(-1) %(-1) (exercise, posthypoxic exposure). A non-dimensional variable, Phi, was used to quantify the interaction present between exercise and hypoxia. The variable Phi fell significantly following the sustained exposure to hypoxia (P < 0.02, ANOVA), indicating that the degree of stimulus interaction between acute hypoxia and exercise had declined. We suggest that the mechanisms by which sustained hypoxia modifies peripheral chemoreflex function may also modify the effects of exercise on the peripheral chemoreflex.