Ability of fresh cigarette smoke from University of Kentucky reference cigarette 2R1 to induce gene conversion, reverse mutation and mitotic crossing-over in strain D 7 of Saccharomyces cerevisiae was examined. A closed cell suspension-recycle system using 2 peristaltic pumps interconnected to a single-port reverse-phase smoking machine was developed to provide complete exposure of cells to smoke within 0.2–10 sec of its generation. The exposed cells showed a dose-dependent increase in the frequency of all the 3 genetic endpoints examined. Cell age was an important factor with younger cells being more sensitive than older. Filtration studies showed that the gas phase possessed as much as 25% of the total whole-smoke activity. Activated charcoal reduced the activity of smoke in direct proportion to its amount in the filter. Acetate filter did not appreciably alter the activity. A comparison of whole smoke from various cigarettes showed that: (1) the nicotine content of a cigarette does not affect the genetic activity of smoke; (2) burley and flue-cured tobaccos have differential activity in gene conversion and reverse mutation systems; and (3) the genetic effects of whole smoke are not peculiar to tobacco pyrolysis because similar effects are produced by smokes from lettuce and other non-tobacco cigarettes. It is concluded that the yeast D 7 system can be used effectively for the quantitative evaluation of genetic effects of smoke from different cigarettes, and both whole cigarette smoke and its gas phase possess mutagenic as well as recombinogenic activity that can be modified by the use of filters.