Nausea/vomiting induced by smoke inhalation is a common phenomenon, possibly explaining why many people who have a naturally strong reaction rarely take up smoking tobacco. The tachykinins are an ancient family of bioactive peptides distinguished by the common C-terminal motif, Phe-X-Gly-Leu-Met-amide. In humans, there are four members: substance P (SP), endokinin (EK) also known as hemokinin (HK), neurokinin A and neurokinin B, which signal through three G protein-coupled neurokinin receptors (NK1-3Rs). Whilst the expression of SP is limited to neural tissue, the EK gene is expressed in lung and placental tumour cell-lines and in many peripheral tissues, including placenta and lung, where EK/HK immunoreactivity has also been detected. As only SP and EK/HK signal strongly through the NK1R, and stimulation of these receptors in the area postrema by peripheral injection of SP induces vomiting in ferrets, placental EK has been proposed as the NK1R agonist that causes morning sickness (The Endocrinologist 115 p26). The nausea and vomiting experienced by patients undergoing cisplatin therapy is alleviated by NK1R antagonists. Using affinity purified antibodies raised against EK (1230) and EK (3241) in a two-site immunometric assay to measure EK-41 in Sepak-extracted plasma, it was found that the blood level of EK-41 in five non-smokers was 1118 pg/ml. In a smoker who hadnt inhaled smoke for two hours, plasma EK-41 was 21 pg/ml; 10 min after smoking, it had increased nearly two-fold to 41 pg/ml, falling to 16 pg/ml two hours later. A non-smokers plasma concentration of EK41 was 16 pg/ml but increased 29-fold to 466 pg/ml 10 min after inhalation of smoke; nausea was experienced two hours later, with levels of EK-41 then at 155 pg/ml. Together, these observations suggest that the lower incidence of nausea/vomiting experienced in both pregnancy and cisplatin therapy in individuals who smoke tobacco may result from downregulation of area postrema NK1Rs by circulating lung endokinin.