Marijuana is widely used, yet few data concerning its actions combined with other drugs exist. Psychologic, respiratory and cardiovascular effects of delta9-tetrahydrocannabinol (THC), the active component of marijuana, combined with oxymorphone (OXM) or with pentobarbital (PBL), were studies in 15 healthy volunteers. Oxymorphone, 1.0 mg/70 kg, iv, caused sedation and ventilatory depression (minute ventilation: 24.9 plus or minus 11.9 SD to 14.1 plus or minus 4.9 1/min with PETCO2 held at 50 torr) in eight volunteers. TCH (27, 40, 60, 90, and 134 mug/kg, iv) increased sedation and further decreased ventilation with each TCH dose to 6.6 plus or minus 3.7 1/min after 134 mug/kg. The combination of OXM and THC decreased the CO2-ventilation slope from 2.23 to 0.88 1/min/torr. When THC, 134 mug/kg, was added to OXM, which alone caused no significant cardiovascular change, cardiac index (4.1 plus or minus 1.3 to 5.0 plus or minus 2.2 1/min/m-2) and heart rate (66 plus or minus 12 to 107 plus or minus 31 beats/min) significantly increased and total peripheral resistance (1,030 plus or minus 260 to 660 plus or minus 200 dynes-sec/cm-5) decreased. Heart rates exceeded 150 beats/min in two subjects after 27 and 134 mug/kg THC. Pentobarbital alone, 100 mg/70 kg, iv, caused no significant ventilatory or cardiovascular change. THC, after PBL pretreatment, induced hallucinations and anxiety in five of seven volunteers; four failed to complete all five doses of THC becuase of the severe psychologic effects. The combination of PBL and 40 to 134 mug/kg THC did not affect ventilation significantly. After PBL pretreatment, THC significantly increased heart rate (76 plus or minus 17 to 130 plus or minus 32 beats/min). Cardiac index also increased (3.8 plus or minus 0.8 to 5.6 plus or minus 1.9 1/min/m-2) and total peripheral resistance decreased (1,070 plus or minus 240 to 720 plus or minus 300 dynes-sec/cm-5). Three subjects developed heart rates esceeding 150 beats/min after 27, 27, and 90 mug/kg THC; in all three, heart rates fell from maximal value with a further dose of THC.