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We developed a quantitative method to estimate long-term chemical-specific pesticide exposures in a large prospective cohort study of more than 58000 pesticide applicators in North Carolina and Iowa. An enrollment questionnaire was administered to applicators to collect basic time- and intensity-related information on pesticide exposure such as mixing condition, duration and frequency of application, application methods and personal protective equipment used. In addition, a detailed take-home questionnaire was administered to collect further intensity- related exposure information such as maintenance or repair of mixing and application equipment, work practices and personal hygiene. More than 40% of the enrolled applicators responded to this detailed take-home questionnaire. Two algorithms were developed to identify applicators’ exposure scenarios using information from the enrollment and take-home questionnaires separately in the calculation of subject-specific intensity of exposure score to individual pesticides. The ‘general algorithm’ used four basic variables (i.e. mixing status, application method, equipment repair status and personal protective equipment use) from the enrollment questionnaire and measurement data from the published pesticide exposure literature to calculate estimated intensity of exposure to individual pesticides for each applicator. The ‘detailed’ algorithm was based on variables in the general algorithm plus additional exposure information from the take-home questionnaire, including types of mixing system used (i.e. enclosed or open), having a tractor with enclosed cab and/or charcoal filter, frequency of washing equipment after application, frequency of replacing old gloves, personal hygiene and changing clothes after a spill. Weighting factors applied in both algorithms were estimated using measurement data from the published pesticide exposure literature and professional judgment. For each study subject, chemical-specific lifetime cumulative pesticide exposure levels were derived by combining intensity of pesticide exposure as calculated by the two algorithms independently and duration/frequency of pesticide use from the questionnaire. Distributions of duration, intensity and cumulative exposure levels of 2,4-D and chlorpyrifos are presented by state, gender, age group and applicator type (i.e. farmer or commercial applicator) for the entire enrollment cohort and for the sub-cohort of applicators who responded to the take-home questionnaire. The distribution patterns of all basic exposure indices (i.e. intensity, duration and cumulative exposure to 2,4-D and chlorpyrifos) by state, gender, age and applicator type were almost identical in two study populations, indicating that the take-home questionnaire sub-cohort of applicators is representative of the entire cohort in terms of exposure.