Cigarette smoking is associated with increases in plasma triglycerides and decreases in plasma high density-lipoprotein-cholesterol concentration. These changes not only increase risk of coronary heart disease but also are secondary to resistance to insulin-stimulated glucose uptake or hyperinsulinaemia. To see whether there is a relation between cigarette smoking and insulin-mediated glucose uptake we measured plasma lipid and lipoprotein concentrations, plasma glucose and insulin response to an oral glucose challenge, and insulin-mediated glucose uptake in 40 matched healthy volunteers (20 non-smokers, 20 smokers). Smokers had significantly higher mean (SEM) very-low-density-lipoprotein triglycerides (0.66 [0.10] vs 0.39 [0.03] mmol/l, p less than 0.02) and cholesterol (0.45 [0.06] vs 0.23 [0.04] mmol/l, p less than 0.005) concentrations and lower high-density-lipoprotein cholesterol concentrations (1.16 [0.05] vs 1.51 [0.08] mmol/l, p less than 0.001). Although plasma glucose concentrations in response to the oral glucose load were similar in the two groups, plasma insulin response of the smokers was significantly higher (p less than 0.001). Finally, smokers had higher steady-state plasma glucose concentrations in response to a continuous infusion of glucose, insulin, and somatostatin (8.4 [0.2] vs 5.0 [0.3] mmol/l, p less than 0.001), despite similar steady-state plasma insulin concentrations. The findings show that chronic cigarette smokers are insulin resistant, hyperinsulinaemic, and dyslipidaemic compared with a matched group of non-smokers, and may help to explain why smoking increases risk of coronary heart disease.