The level of alpha-fetoprotein (AFP) gene expression during liver regeneration in mice is regulated by the Afr2 gene. C3H/HeJ mice express 10-fold higher levels of AFP than C57BL/6J mice. We show that AFP gene expression is not Afr2 regulated after intoxication with the carcinogen diethylnitrosamine (DEN). Peak levels of AFP gene expression of the 2 strains were identical, although reached at different times following treatment. Analysis of the expression of AFP derived transgenes not subject to Afr2 regulation and genetic analyses showed that the difference in timing of peak AFP gene expression after DEN intoxication was independent of Afr2 regulation.