1. The effects of the intravenous injection of isoprenaline on heart rate and arterial pressure has been studied in dogs artificially respired with room air or with 12% oxygen-88% nitrogen.2. In dogs breathing room air, isoprenaline in doses from 0.02 to 500 mug/kg increased heart rate and reduced arterial pressure. Ventricular fibrillation was produced in one out of three dogs given 250 mug/kg. This was the only dog breathing room air which was killed by isoprenaline.3. In dogs breathing room air the repeated intravenous injection at 5-min intervals of 2.5 mug/kg increased heart rate and reduced arterial pressure. No ill effects were produced by six doses.4. In dogs respired with 12% oxygen-88% nitrogen the PaO(2) was reduced from 84 to 38 mm Hg with no changes in PaCO(2). In these dogs death was produced by doses of isoprenaline which in dogs breathing room air produced normal responses.5. The fatal dose of isoprenaline (10-50 mug/kg) reduced heart rate and arterial and pulse pressures; sinus rhythm persisted until arterial pressure was less than 50 mm Hg. Ventricular fibrillation did not occur; death occurred from cardiac asystole.6. Death was produced in a similar way in dogs with hypoxaemia by giving four or five doses of isoprenaline (2.5 mug/kg) at 5-min intervals or by two doses of 25 mug/kg.7. The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility.8. These lethal effects of isoprenaline could be prevented by pretreatment with propranolol.