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Amoscanate (0.1% w/v) in methanol solution applied to skin by tail immersion 1 day prior to cercarial exposure provided mice with better than 90% protection against mature Schistosoma mansoni infections. Cercariae penetrated and schistosomula migrated from treated skins as readily as in control skins. Lung incubation assays, however, indicated that day 7 lung worm burdens were only about half those of control values. By day 20, worm burdens were reduced further to approximately 15% of those for control mice. The delayed prophylactic activity was apparently not due to percutaneously absorbed compound. Wipe application of amoscanate to the skin was nearly as effective as immersion.