In drosophila, molecular determinants from fungi and Gram-positive bacteria are detected by circulating pattern-recognition receptors. Published findings suggest that such pattern-recognition receptors activate as-yet-unidentified serine-protease cascades that culminate in the cleavage of Spätzle, the endogenous Toll receptor ligand, and trigger the immune response. We demonstrate here that the protease Grass defines a common activation cascade for the detection of fungi and Gram-positive bacteria mediated by pattern-recognition receptors. The serine protease Persephone, shown before to be specific for fungal detection in a cascade activated by secreted fungal proteases, was also required for the sensing of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a parallel proteolytic cascade activated by 'danger signals' such as abnormal proteolytic activities.