The Salmonella typhimurium microsomal test system for mutagenic activity was successfully used to detect the presence of mutagenic compounds in the smoke condensates of several types of cigarettes. The condensates were shown to contain compounds which could cause frameshift mutations when activated by microsomal enzymes. An analysis of fractions of smoke condensate revealed that the detected mutagenic activity was distributed in several of the fractions. Most of the activity of the whole condensate was in basic fractions and in a weakly acidic fraction. Condensates from cigarettes treated with magnesium nitrate differed from other condensates in two respects. They contained frameshift mutagens which did not require microsomal activation and mutagens which could cause base-pair substitution mutations. Although the detection system usually employs rat liver microsomal preparations, a rat lung microsomal preparation was also found to be capable of converting smoke condensates and known chemical carcinogens into mutagenic forms.