The National Exposure Registry of the Agency for Toxic Substances and Disease Registry (ATSDR) uses standard methods to study human exposure in four chemical subregistries: trichloroethylene (TCE), dioxin, benzene, and trichloroethane. The TCE Subregistry includes a baseline cohort of 4006 white registrants with drinking water exposure in Michigan, Indiana, Illinois, Pennsylvania, and Arizona. Between 3 and 6 follow-ups per site were conducted from 1989 to 2000, after baseline. Standardized morbidity ratios, controlling for age and sex, compared prevalences of 16 general health conditions in the subregistry with aggregated national estimates from the 1989-1994 National Health Interview surveys. Excess cases of dermatologic, hematologic, or hepatic disorders and strokes persisted over the lifetime of the registry. Persistent excess urinary tract disorders are likely caused by a systematic bias. This review of first-generation methods may be used to strengthen future exposure registries.