The major predictors of health risk from pesticide exposure are quantity and toxicity of pesticides reaching end-users, field workers, and persons (including children) with casual and indirect exposures to field and food residues, drift, and contaminated groundwater. Past work in Israel and the Palestinian National Authority has documented risks for acute poisoning, daily illness, transient neurotoxic effects, and potential cancer hazards in workers, populations exposed to pesticide drift, and the general population. Risk assessment predicts that reduction in use of agents with high toxicity and pesticide substitution are desired strategies for achieving the largest reductions in risk, but successful implementation and program sustainability depend on maintaining crop yield and increasing farmer earnings. A joint pilot Israeli-Palestinian-NGO program aims to determine whether crop yields and profits can be sustained while reducing pesticide use, promoting integrated pest management, and restricting ecosystem damage. The project involves six components: (1) assessments of health risk and crop yield in relation to pesticide use and exposure; (2) training health-agricultural teams to introduce and evaluate crop growth and managements with reduced pesticide use; (3) tracing and stopping import and trade in banned or restricted pesticides; (4) restricting child labor; (5) promoting information delivery and worker and community right-to-know and right-to-act; and (6) establishing a uniform regional standard for protection of workers and the general public. Preliminary evidence (organochlorines and breast cancer, organophosphates and illness in field workers) indicates that (1) a reduction of use is the foremost determinant of a reduction in health risk; (2) cotton yield can be increased despite a reduction in pesticide use (organophosphates); and (3) a reduction in pesticide use (organophosphates and organochlorines) has to be part of a crop rotation program for food crops timed to seasonal fluctuations in supply, demand, and crop price.