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Interbreeding between hycanthone-resistant and hycanthone-sensitive schistosomes was achieved using a worm transfer technique which considerably reduced the length and the complexity of the operations generally involved in performing schistosome genetic crosses. A mouse was considered to harbor resistant schistosomes if, three weeks or more after a single intramuscular injection of 80 mg/kg hycanthone schistosome eggs were still excreted in the feces, at least one normal worm pair was obtained by perfusion, or miracidia could be seen hatching from the liver. The F1 hybrid progeny from crosses between sensitive and resistant schistosomes proved to be sensitive to hycanthone, irrespective of whether the resistant parent was the male or the female. The resistant phenotype reappeared in back-crosses and in the F2 progeny. These results could be confirmed using the traditional technique of single sex infections. It can thus be concluded that hycanthone resistance behaves like an autosomal recessive trait. These results suggest that hycanthone-resistant schistosomes are deficient in some factor, possibly an enzymatic activity which transforms hycanthone into a biologically active molecule, as suggested in a recent hypothesis on the mode of action of hycanthone.