Dose monitoring of exogenous methylators by measurement of N-methylvaline in hemoglobin (Hb) is rendered difficult due to a relatively high, variable background in unexposed persons. A kinetic study indicates intracellular S-adenosylmethionine to be a main source of these background methylations. A comparison of twin pairs indicates that the variation in methylvaline levels is partly hereditary (P less than 0.001). Therefore, in a study of monozygotic twin pairs discordant for tobacco smoking the resolving power of the monitoring was increased and in vivo doses of methylators from the smoke could be more easily monitored through their adducts to Hb. Probably, twin studies offer a useful tool for the identification and quantification of electrophiles of endogenous and exogenous origin.