1. Respiratory and circulatory effects of phenyldiguanide (PDG), sodium cyanide and lobeline have been studied in eighteen patients.
2. PDG, when injected into the main pulmonary artery, produced stimulation of breathing together with bradycardia and hypotension. A mean injection-response time of 5·2 s was close to the pulmonary artery-ear lobe circulation time in the same patients.
3. Sodium cyanide produced respiratory and circulatory effects similar to PDG and with the same injection-response time. It was concluded that both drugs act on the carotid body.
4. Lobeline sulphate produced apnoea with or without cough in twelve of the fifteen patients studied, with a mean injection-response time of 2·1 s; this was shorter than the pulmonary artery-ear lobe circulation time. This response preceded the well-known hyperpnoea.
5. The short injection-response time of lobeline is consistent with the hypothesis that lobeline stimulates pulmonary receptors before it acts on the carotid bodies, and that there are receptors in the human lung that are depolarized by chemical agents.
6. The cough response was replaced by apnoea when the dose of lobeline was decreased.
7. Whereas PDG did not produce any abnormal sensation in the body, lobeline caused a sensation of fumes or smoke in the lower throat or burning over the manubrium sterni. Neither drug produced a sensation of breathlessness.