Previous observations of mosquito blood feedings have focused on Aedes aegypti mosquitoes feeding on the leg of a frog or the ear of a mouse. The path followed by the mosquito��s mouthparts under the skin was explained with photographs and drawings. In this study, we studied the behavior of Anopheles gambiae and its consequences for mouse skin physiology and parasite transmission. We used Plasmodium as our model organism for Lomitapide Mesylate studies of pathogen transmission. Malaria affects 40% of the world��s population, in tropical and subtropical regions. A mouse model of infection with this parasite is available and was used in this study. We used intravital videomicroscopy to analyze the feeding behavior of Anopheles gambiae. We observed the mosquito feeding through the skin of the back of an anesthetized mouse, as described by Petit. The mice were either naive, or had been passively or actively immunized with Anopheles gambiae saliva. The reaction of the skin to Anopheles gambiae blood feedings was followed over time by histological observation. Immunohistochemistry was used to localize the release of saliva and sporozoites, and to follow the course of saliva and sporozoite detection in the skin. Previously reported observations of mosquito bites have mostly concerned bites to frog legs or mouse ears. We used a less specialized model than the ear, which contains cartilage and has a thin skin unlike that covering the rest of the body. We also felt that the observation of Anopheles gambiae mosquitoes biting a mammalian host would be the most appropriate model for obtaining useful data concerning biting and parasite interactions. Our observations are supported by video recordings, still photographs and sections through the tissues of bitten mice. They enabled us to describe in more detail the interaction between Anopheles gambiae and the skin of naive or saliva-sensitized mice. We also used mosquitoes infected with Plasmodium berghei and various tools, including antibodies and fluorescent strains, to study parasite transmission. Videos of the movement of the mosquitoes�� mouthparts within the skin revealed that the tip of the labrum was highly flexible during the probing phase. A large area under the skin was probed, without the mosquito having to withdraw its proboscis or change the point of entry. Similar observations were previously reported by for Aedes aegypti feeding on the webbed skin of frogs. The Mepiroxol labral elevator and retractor muscles probably play a major role in this flexibility. Interestingly, our observations also suggest that the localization of blood vessels by mosquitoes may be fortuitous. Despite the use of a different experimental set-up and model animal, Gordon and Lumsden also concluded that chance played a major role in blood detection. However, our experiments were performed with laboratory-reared insects and the rapid location of blood vessels is a trait known not to be maintained in the laboratory We recorded the blood feeding phase. Young mosquitoes fed more rapidly than older mosquitoes and Anopheles gambiae was found to behave essentially as a capillary feeding insect to achieve repletion. Blood feeding by mosquitoes to repletion was one important aspect in the escape of larvae for W. bancrofti transmission. Pool feeding was observed on some occasions but was not efficient and did not result in repletion. These observations contrast with those for blood feeding by Aedes aegypti, which can become fully engorged after pool feeding. Parasitization has been reported to change insect behavior.