Studies of outbreaks of methylmercury poisoning in Japan and Iraq from consumption of methylmercury (MeHg)-contaminated fish or bread proved that brain was the target organ, the toxic effects were dose-related, and the fetal brain was especially susceptible. Previous population studies suggested that a 5% risk of minimal fetal effect may be associated with a maternal hair mercury concentration during pregnancy of 10-20 ppm (mu g/g), a level that can be readily achieved by frequent consumers of fish. However, these studies had limitations, and as a result no definite conclusion concerning the lowest effect level could be reached and the question of a possible hazard to public health remained unanswered. There was a clear need for a more definitive study that would be prospective, involve a large enough cohort for risk analysis and adhere to accepted epidemiological principles. An appropriate site for such a study is the Republic of Seychelles, a location that afforded successful collaboration between the Seychelles Ministry of Health and faculty of the University of Rochester. A pilot study of 804 infant-mother pairs was followed by a main study of 779 mother-infant pairs. In the pilot study children were examined once between 5 and 109 weeks of age; in the main study they are being evaluated longitudinally starting at 6 1/2 months of age. This paper introduces both the pilot and main studies, describes their design, and summarizes the findings through 6 1/2 months of age. When the Seychelles study is completed, the analyses will provide a database for those nations that choose to regulate their citizens' fish consumption and/or provide dietary education.