To our knowledge, there is no information about the complement system operation at pHs different from 7.4. If the complement is really dangerous to the insects in order to “force” them to produce inhibitors, complement should be active in the midgut conditions such as in pHs around 7.0 in triatomines and even in alkaline environments as in the abdominal midgut from some mosquito species where the pH reaches values equal or higher than 8.0 after a blood meal. Once the intestinal epithelium from insects has a unique cell layer, the damage caused by complement activation could lead to the GDC-0879 rupture of the digestive tract and even death of the insect. The results obtained here about the performance of the complement system at different pHs show that the classical and Doxorubicin alternative pathways are active at the pH 7.16, inside the anterior midgut from triatomines, and even at pH,8.0, inside the midgut of mosquitoes. It is possible that, under these circumstances, the alternative pathway would be triggered by carbohydrates from the glycocalix of the intestinal cells and that the classical pathway would be triggered by unspecific binding of natural antibodies to these carbohydrates or other intestinal molecules. The presence of carbohydrates covering the intestinal membranes could trigger the lectin pathway by binding the MBL protein. Figure 4 contains a scheme of the complement activation process in both, classical and alternative pathways and shows the MAC formation by the action of C3 convertases. C3 convertases also operates as C5 convertases. To the sake of simplicity, the activation of the lectin pathway was omitted. The MannamBinding Lectin pathway is not activated by any of the protocols used for the inhibitory assays in the present work. Therefore, the results obtained had no influence from this pathway. The red marks in the scheme indicate the most probable points where the salivary and/or intestinal inhibitors may be acting along the complement cascade taking into account the results observed in Tables 1 and 2. The inhibition of the C4b deposition in the classical pathway indicates a possible action over C1r and/or C1s, by inhibiting their proteolytic action as is performed by the soluble C1 inhibitor present in the normal sera. The blockage of C3b deposition in the classical pathway could be attributed to the action of the inhibitors in any point mentioned before or in the C2a proteolytic activity over C3. The presence of any factor accelerating the C2a decay from the C4bC2a-C3b complex could also lead to the same result. An inhibitor able to accelerate the decay of C2a would be similar to the C4 binding protein, which is found soluble in the normal sera. C4bp accelerates the C2a decay from the C4b-C2a-C3b complex and acts as cofactor in the cleavage of C4b by factor I, another soluble regulatory protein. The inhibition of C3b deposition in the alternative pathway could be explained by the direct inhibition of protease D. Protease D is a soluble enzyme, already active in the blood, which has higher specificity to activate factor B, by proteolysis, when it is associated to C3b opsonized to the activator surface or when it is part of the soluble complex B-C3-H2O. The activated factor B is another protease able to activate C3 to C3b and C3a. Bb inhibition could also promote reduction in C3b deposition onto activator surfaces. Any molecule, present in saliva or intestinal contents from insects, acting over the C3b-Bb-C3b complex and accelerating the decay of Bb would also favour the reduction of C3b deposition in the alternative pathway. Although the material obtained from midgut microvillosities are not able to inhibit C3b deposition by the classical pathway, we can not discard the possible presence of a MAC-assembling inhibitor inserted on the midgut membranes, as observed on erythrocytes 