Cigarettes with selective reductions in nicotine delivery have been considered as potential tools to prevent or treat nicotine dependence or to reduce harm by virtue of reduced nicotine and nitrosamine delivery. An important question is whether individuals smoke these products more intensively, as has been shown to occur with ventilated-filter cigarettes. To investigate this issue, we compared conventional highly ventilated filter cigarettes, having very low tar and nicotine yields when smoked by Federal Trade Commission method (1 mg tar, 2 mg carbon monoxide [CO], .2 mg nicotine), with low nicotine content cigarettes, manufactured from a genetically modified strain of tobacco, which had higher tar but lower nicotine yield (14 mg tar, 13 mg CO, .02 mg nicotine). A total of 16 cigarette smokers participated in two 8-hr sessions (order counterbalanced) during which they smoked each type of cigarette ad libitum. Expired-air CO, plasma nicotine, and smoking topography measures were collected. Subjects showed significant increases in smoking when using the highly ventilated filter cigarettes, and puff volume was significantly greater than with the low nicotine content cigarettes. Subjects achieved an expired-air CO level 74% as high as with the low nicotine content cigarettes; the latter produced CO levels similar to those measured at baseline when subjects smoked their habitual brands of cigarettes. Plasma nicotine levels obtained when subjects smoked the highly ventilated filter cigarettes also were significantly higher than when they smoked the low nicotine content cigarettes. These results indicate that the delivery of substantial amounts of smoke, with selective reductions in nicotine yield, appears to prevent compensatory smoking behavior. Further studies should determine whether similar results are obtained in naturalistic environments.