A number of promutagenic exocyclic DNA adducts have recently been detected in both humans and rodents without carcinogen treatment These observations raised questions about their origins and potential significance in carcinogenesis. In this commentary, we present our views pertaining to the in vivo sources of these cyclic adducts, specifically the cyclic propano and etheno adducts. The basis for our discussion comes mainly from the information generated through a span of more than a decade from several laboratories, including ours. This commentary summarizes the data from the chemical and biochemical studies that provide support for the hypothesis that lipid peroxida-tion is involved in the endogenous formation of these exocyclic adducts.