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Sixteen persons providing a diversity of previous exposures were challenged by bite with Aedes aegypti and with at least two species of anopheline mosquito. Immediate and delayed skin reactions were recorded. The subjects fell conveniently into three categories: 1) nonsensitized, 2) sensitized, and 3) desensitized according to their respective reactions to specific mosquito bites and their history of exposure. Persons with no prior deliberate exposure to particular mosquito bites exhibited a delayed but little immediate response, whereas those with deliberate or prolonged exposures displayed varying degrees of both immediate and delayed responses or loss of reactivity. Six of the seven nonsensitized persons showed little difference in the extent of their delayed reactions to various species. One highly allergic person provided a good example of the role of individual susceptibilities in the skin response to mosquito bites. Another subject appeared to represent a case of nonreactivity due to age. Instances of both cross-reactivity and specificity between the two genera and among the anopheline species were noted in the immediate and the delayed response of sensitized persons and in the loss of these responses in desensitized persons. The observation of the disappearance of both the immediate and the delayed response in those deliberately exposed to mosquito bites for only a relatively short period of time (less than a year) is of significance in view of the report by others that a desensitized state leading to the loss of the immediate reaction requires an exposure of many years.