Aflatoxin Q1 8,9-oxide was synthesized and found to yield lower levels of N7-guanyl adducts than obtained from aflatoxin B1 8,9-oxide when mixed with calf thymus DNA or Salmonella typhimurium TA 98 cells. However, when S. typhimurium TA 98 was treated with the (analogous) epoxides of aflatoxin B1, aflatoxin G1, aflatoxin Q1, or sterigmatocystin, the ratios of revertants to N7-guanyl DNA adducts were similar. Aflatoxin Q1 and aflatoxin B1 8,9-oxide (trapped here as the glutathione conjugate) are the major oxidative products formed from aflatoxin B1 at all substrate concentrations in human liver microsomes, and cytochrome P-450 (P-450) 3A4 appears to be the dominant enzyme involved in both oxidations, as judged by studies involving correlation of activities in different liver samples, chemical inhibition, immunoinhibition, and reconstitution with purified hepatic and yeast recombinant P-450 3A4. Aflatoxin Q1 is not appreciably oxidized in human liver microsomes and is not very genotoxic. The postulated formation of both aflatoxin Q1 and aflatoxin 8,9-oxide from aflatoxin B1 can be rationalized by a model in which P-450 3A4 binds the substrate in either of two different configurations. This is further demonstrated by the dichotomous effect of 7,8-benzoflavone--this flavone stimulates 8,9-epoxidation while inhibiting the 3 alpha-hydroxylation reaction to form aflatoxin Q1. Thus, the 3 alpha-hydroxylation of aflatoxin B1 to aflatoxin Q1 is viewed as a potentially significant detoxication pathway.