Marijuana is a sedative, and most sedatives are respiratory depressants. However, the ventilatory effects of marijuana are unknown. In a placebo-controlled study of 8 subjects, smoking marijuana significantly increased ventilation and hypercapnic ventilatory response. Peak effects occurred 15 min after smoking, when ventilation increased from 7.4 +/- 0.39 (mean +/- SE) to 10.4 +/- 1.41 liter per min (P less than 0.01), whereas hypercapnic ventilatory response, measured as the slope of the relationship of ventilation to CO2, increased from 2.7 +/- 0.28 to 5.4 +/- 1.02 liter per min per mm Hg (P less than 0.05). Blood pH, PCO2, and ventilatory response to hypoxia were unchanged. Changes in ventilation usually parallel changes in metabolic rate. Smoked marijuana caused an increase in metabolic rate that also peaked after 15 min. Pretreatment with propranolol completely abolished the increase in hypercapnic ventilatory response, but did not affect the other changes. Thus, smoked marijuana had stimulatory effects on metabolic rate, ventilation, and the ventilatory response to CO2. The latter appears to be mediated by the beta sympathetic nervous system.