The systemic effect of bupivacaine on the control of ventilation was studied in eight ASA I (six male, two female) unpremedicated healthy subjects aged 30–55 yr (mean 43.5 yr) and weighing 59–82 kg (mean 69 kg) after axillary blockade with bupivacaine 0.5% without epinephrine, 3 mg/kg. The slope of the ventilatory response to CO2was significantly increased (P< 0.05) from its control value (1.77 ± 1.03 1 ± min−1· mmHg−1[mean ± SD]) 30 min (+19 ± 32%) and 60 min (+32 ± 37%) after axillary blockade, while plasma bupivacaine levels were 1.65 ± 0.82 and 1.40 ± 0.60 μg/ml, respectively. The correlation between individual plasma bupivacaine levels and the changes in the slope of the ventilatory response to CO2was significant (r = 0.57, n = 16,P< 0.05). Resting minute ventilation and end-tidal CO2values did not change significantly. These results suggest that bupivacaine has a systemic stimulating effect on the ventilatory control mechanisms.