The mechanisms responsible for the marked increase in ventilation at the onset of exercise are incompletely defined. A conditioned response to exercise anticipation has been suggested as an influencing factor, but systematic measurements have not been made during the transition from rest to the time when exercise is anticipated but has not yet commenced. We tested the hypothesis that cortical activity associated with the anticipation of exercise causes hyperpnea, which is at least partly responsible for the increased ventilation at the onset of exercise. To assess the influence of continuous cortical activity in the absence of exercise anticipation the subjects performed mental arithmetic tasks. Fifteen subjects performed the two experiments in a random order. Ventilation was measured noninvasively using a calibrated respiratory inductive plethysmograph and end-tidal CO2 concentration (FETCO2) was monitored at the nasal vestibule. Both exercise anticipation and mental arithmetic caused an increase in minute ventilation (VI) (P less than 0.01) and mean inspiratory flow (VT/TI, P less than 0.01), which reflects respiratory center drive, although the derivation differed in that the former was volume based, whereas the latter was due to alteration in timing. Despite the increase in VI, FETCO2 remained constant in both instances. In a complementary study the constant FETCO2 in the face of increased VI was shown to be due to increased CO2 output. The results show that the mere anticipation of exercise causes an increase in ventilation. The mechanism responsible for this hyperpnea cannot be due solely to respiratory center activation because of the constancy of FETCO2 and the associated alterations in cardiac and metabolic behavior.