The present study examined the situation-specific effects of smoking using a paced regimen of smoking to control the smoke intake. The subjects were first required to sham smoke and then actually smoke one of their cigarettes in two different test contexts: 1) in the laboratory where they had never previously smoked and 2) at home, alone in a quiet room where they regularly smoke. Light (< 10 cigarettes/day) and heavy smokers (> 15 cigarettes/day) were studied to test for a possible effect of the paced regimen itself. In the light smokers, smoking produced a larger increase in heart rate (HR) in the laboratory than in the natural smoking environment; however, in the heavy smokers the smoking had a larger effect in the normal smoking environment than in the laboratory. There were no significant group or test situation differences for baseline HR, skin conductance and finger temperature. The groups also did not differ in the intensity of drawing on the cigarette or inhaling, as indicated by a puff sensor and a respiratory belt, respectively. It was concluded that differences between the effects of a cigarette in a laboratory setting and in a natural smoking environment may reflect pharmacodynamic effects of smoking that are modified by the subjects' prior experience with smoking. The data are discussed with regard to conditioned tolerance to the effect of smoking.