Research at the University of Rochester (U of R) has been focused on mercury for nearly half a century. Initially studies focused on dosimetry, especially the accuracy of measuring exposure, and experimental work with animal models. Clinical studies in human populations started when the U of R mercury group was asked to assist with dosimetry in the Iraq epidemic of 1971-1972. Initial clinical studies described the effects of methylmercury (MeHg) poisoning on adults and children. A dose-response curve for prenatal exposure was determined and it suggested that relatively low exposures might be harmful to the fetus. Since most human exposure to MeHg is dietary from fish consumption, these theoretical dangers had far-reaching implications. After Iraq, the Rochester team pursued exposure from fish consumption in both adults and children. Populations with high fish consumption were identified in Samoa and Peru for studying adults and in Peru and the Seychelles islands for studying children. The possible health threat to the fetus from maternal fish consumption quickly became the focus of research efforts. This paper reviews the Rochester experience in studying human exposure to MeHg from fish consumption.