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Schistosomiasis continues to plague populations living in disease-endemic areas, and exposure to infective cercariae results in more than 200 million cases worldwide. Laboratory experiments were conducted to test whether a cercaricidal film applied directly to the water surface can reduce viability of cercariae. A distillate from inexpensive cedarwood oil enriched for cedrol in a mixed oil fraction was formulated (1:5) with the surfactant Tween 80. When applied to the surface of clean and turbid water in test vessels, the formulation spread across and just below the air-water interface, causing inactivation of Schistosoma mansoni cercariae within minutes. The active ingredient was heat stable and reduced schistosome survival and infectivity by 90% and 99.2%, respectively in a mouse model. The effective dose (13 μg/cm2) was dependent on surface area rather than volume of water treated. We conclude that application of the biodegradable formulation to the surface of schistosome-infested waters may be an effective, economical, and safe means of reducing human infections.