Serum and salivary cotinine levels were determined in tobacco smokers (n=125) tobacco (n=47) or who smoked both marijuana and tobacco (n=78) as part of a field study of the pulmonary effects of heavy, habitual use of marijuana alone or with tobacco. After adjustment for current daily amount of tobacco use and time since the last tobacco cigarette was smoked, the smokers of both marijuana and tobacco were found to have lower levels of cotinine then those who smoked only tobacco, in serum [258±113 ng/ml (S.D.) and 332±109, respectively; p=0.003] and in saliva (331±170 and 395±170, respectively; p=0.058). Serum cotinine showed a significantly negative relationship to the daily amount of marijuana currently smoked ( p=0.026). Possible explanations include inhibition by marijuana component(s) of the enzymes that participate in the conversion of nicotine to cotinine, differences in nicotine absorption patterns between the two groups of tobacco smokers, and acceleration of cotinine metabolism by marijuana smoking. Carefully controlled pharmacokinetic studies, not possible in a large-scale survey such as this one, are required both to confirm the differences in blood cotinine levels observed between the dual smokers of tobacco only and to define more clearly nicotine-marijuana interactions.