GAO reviewed U.S. participation with developing countries and international organizations in programs to combat malaria and in efforts to develop effective vaccines and drugs to: (1) obtain an overview of the U.S. investment in combating malaria; and (2) examine current program activities in light of existing policies, strategies, and the prevalence of malaria. Primary health care systems in developing countries are rapidly becoming the principal means of providing the necessary facilities to diagnose, treat, and report the occurrence of malaria. Through this means, more extensive efforts are being made to provide anti-malaria drugs to prevent and reduce the mortality and morbidity rates due to the disease. However, GAO found that there has been a decline in the level of U.S. assistance to anti-malaria activities. As this decline continues, the United States should protect its anti-malaria investments in terms of gains already achieved, or prevent the disease from becoming a detriment to other development programs. Toward this end, the Agency for International Development (AID) established and continues to support a network of scientists to develop a vaccine to combat the disease. GAO also found that the constraints to effective anti-malaria activities must be fully considered to ensure efficient use of limited foreign assistance resources. AID should avoid those situations where the inherent constraints cannot be resolved by the design of the projects and where external constraints preclude long-term effectiveness. GAO concluded that the resurgence of malaria in the past decade, new approaches involving primary health care services, and the decline of United States assistance warrants a reexamination and update of AID anti-malaria guidelines.