While urinary cotinine is the nicotine metabolite most commonly utilized to quantify nicotine intake, many additional nicotine metabolites have been identified and quantified in urine samples. Data from two studies involving smokers and snuff users are analyzed to address estimation of nicotine intake using urinary and salivary nicotine metabolites. Without precisely known dosage, nicotine intake is approximated as a linear combination of urinary nicotine and seven urinary nicotine metabolites. Comprehensive regression modeling is performed to determine what combinations of urinary nicotine metabolites provide better estimation of nicotine intake in these subjects than the predominant practice of analyzing only urinary cotinine. Variability, both within subjects (between measurements) and between subjects, is examined with regard to reliability of measurement and replicate sampling. Salivary cotinine models are compared to urinary metabolite models. Results suggest that estimation of nicotine intake is greatly improved by measuring urinary cotinine and additional metabolites (trans-3'-hydroxycotinine, and glucuronide conjugates) over measuring only cotinine. Analyses also indicate that replicate sampling on subject greatly improves the reliability of the measurement. Based on these data, a model to predict nicotine equivalents based on saliva cotinine was severely inferior to any of the urinary models, including that of urinary cotinine alone.