From 1994 through 1996, federal, state, and nongovernmental organizations in Mexico and in the United States of America developed and piloted a Binational Health Information System for Epidemiological Surveillance of Mexican migrant workers. The system allowed data exchange for epidemiological surveillance between the state of Guanajuato in Mexico and the Commonwealth (state) of Pennsylvania in the United States, for case detection, prevention, and treatment, through shared contact investigation and case management of communicable diseases. The target population consisted of migrant workers traveling between Guanajuato and Pennsylvania to work mainly in the mushroom industry, and their sexual partners in their Mexican communities of origin. Computerized migrant health information modules were set up in Guanajuato and in Pennsylvania. Patient information and epidemiological surveillance data were encrypted and communicated electronically between the modules, using the WONDER communications system of the U.S. Centers for Disease Control and Prevention. Evaluation of the Guanajuato-Pennsylvania Binational Health Information System showed that major barriers to binational epidemiological surveillance and control are: a) lack of communication binationally; b) interrupted medical care due to migration; c) inconsistent diagnosis and treatment criteria between the two countries; d) lack of referral clinical records from one country to the other; and e) deficient legal regulations concerning binational clinical data transfer. To our knowledge, this is the first project that has successfully demonstrated the technological feasibility of a binational disease control system linking a state in the interior of one country with a state in the interior of another country, rather than just states in the border region. The project also advanced the understanding of health service organizational issues that facilitate or hinder communication, outreach, disease prevention, and organization of health care services for migrant workers in both Mexico and the United States. Despite the unprecedented success and potential bilateral benefits demonstrated by this project, serious structural and organizational deficits in the public health systems of both countries must be addressed before epidemiological surveillance can be achieved binationally.