The acute effect of inhaling the smoke of three cigarettes was compared to the effect of inhalation of an amount of carbon monoxide (CO), giving the same CO-saturation of the arterial blood as smoking during rest and during maximal exercise on a Krogh cycle ergometer. Sixteen male subjects were tested in the morning (1) after about 8 h without smoking (control), (2) after inhalation of the smoke of three cigarettes (smoke), and (3) after CO-inhalation (CO). It was found that the average maximal rate of O2-uptake (VO2 max) decreased during both smoke and CO by about 7%. Endurance time at VO2 max decreased 20% during smoke but only 10% during CO. A significant decrease in maximal heart rate (HR), and an increase in HR at rest, was demonstrated only during smoke. The peak lactate concentration (HLa) following maximal exercise was significantly decreased after smoke. The results suggest that the decrease in VO2 max during smoke is due to the CO-saturation of the blood, and hence to a decrease in the oxygen capacity of the blood, while the decrease in endurance time during smoke is combined effect of the CO-saturation and an increased cost of breathing caused by the smoke particles. It is further suggested that nicotine, or possibly some other components of the smoke, have an enhancing effect on the heart at rest rest, while an inhibition is seen during maximal exercise.