The biological activity of smoke from a novel, electrically heated cigarette prototype is compared to that of conventional cigarettes. This novel cigarette is designed to be used in constant contact with a battery-operated lighter as an external heat source instead of continuously burning tobacco. The lighter consists of a series of eight heater blades which supply computer controlled energy, sufficient to maintain temperature and time limited distillation and pyrolysis without igniting the cigarette. The cigarette is made of conventional tobacco filler rolled into tobacco mat for optimal heat contact and non-destructive cigarette removal. Due to the enclosed aerosol generation, the new cigarette type generates essentially no sidestream smoke. The mainstream smoke differs substantially in its chemical composition and its biological activity from smoke of the 1R4F Kentucky reference cigarette, which approximates the middle of the US marketplace in tar delivery. Compared to the yields of the 1R4F, many cigarette smoke constituents are significantly reduced (e.g., total particulate matter by 60%, carbon monoxide by 94%, benzene by 98%, benzo(a)pyrene by more than 98%, tobacco-specific nitrosamines by 83%). Correspondingly, mainstream smoke from the novel cigarette type shows a lower biological potency when compared to the reference cigarette: Bacterial mutagenicity by 97%, in vitro cytotoxicity by 80%, and in vivo irritancy by more than 60%.