Acrolein and formaldehyde, as well as acetaldehyde, are currently regarded as important toxicants in cigarette smoke. In this study with rats, previously-reported protectants against acetaldehyde were tested for their effectivity as protectants against acrolein and formaldehyde. As with acetaldehyde, pretreatment with high oral doses ofl-ascorbic acid,l-cysteine, and a combination of these protectants in reduced amounts with thiamin gave a high degree of protection against lethal doses of acrolein. Survivors after 72 hours were in the 90% range compared to survivors of pretreated saline controls in the 5% range. With equimolar doses of adrenergic-blocking agents, protection against acrolein after 72 hours was greater with an alpha-blocker, e.g. phenoxybenzamine (60% survivors), than with a betablocker, e.g. propranol l (15% survivors). Protection withl-ascrobic acid was dose-related and also additive with the adrenergic-blocking agents. With above protectants, protection against acrolein was as good, if not better, than against acetaldehyde. Protection against formaldehyde after 72 hours was only partial, being highest forl-ascorbic acid (55% survivors) compared to saline controls (5% survivors). Less effective against formaldehyde werel-cysteine (20% survivors) and phenoxybenzamine (15% survivors). Propranolol gave no protection against formaldehyde. It is speculated that in vivo protection byl-ascorbic acid andl-cysteine could occurdirectly by detoxification of the aldehyde toxicants orindirectly by normalizing the synthesis or release of tissue catecholamines abnormally altered by the aldehyde toxicants. Further animal experimentation is necessary before any extrapolation of these findings for human use can be considered.