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Ingestion of arsenic in drinking water has been linked with the risk of urinary bladder cancer, however, questions remain about the characterization of the dose-response relationships, ranges in induction-latency intervals, and whether there are critical lifetime exposure periods of heightened susceptibility. In southeastern Michigan, approximately 235,000 people are exposed to arsenic concentrations above the new maximum contaminant limit (10 mug/L) in their home drinking water. The risks from these moderately elevated arsenic concentrations are being investigated in a population-based bladder cancer case-control study in eleven counties of southeastern Michigan. Water samples were collected and analyzed for arsenic at current residences, and inorganic arsenic concentrations were estimated at past residences and workplaces, and in select foods. Questionnaires were used to obtain residential and occupational mobility, dietary habits, and smoking history from participants. Individual-level estimates of arsenic exposure were calculated using a newly developed Space-Time Information System. This methodology integrates sources of spatial, temporal, and spatio-temporal variability in an assessment of lifetime exposure to arsenic. Fluid and food consumption data were joined with mobility histories and arsenic concentrations to generate the most comprehensive lifetime assessment of arsenic exposure conducted to date. Average cumulative intake of arsenic over the adult life-course ranged from 2.53*104-1.30*10 5 mug, depending on which parameters were included in the exposure metric. Various methodological approaches were highlighted for evaluating the relationship between arsenic exposure and bladder cancer over the life-course. Temporal visualization techniques and temporally-specific unconditional logistic regression analyses were demonstrated using both participant's age and calendar year as measures of time. An approach for analyzing yearly averages of arsenic exposure is introduced, and compared with more traditional dose metrics such as cumulative exposure, current exposure, and decade-long time windows of exposure. These methods will be adopted when data collection is complete to assess the relationship between arsenic exposure and bladder cancer over the life-course. Results from this study will assist scientists and policy-makers in ascertaining a safe concentration of arsenic in drinking water.