The extent and rate of development of Plasmodium gallinaceum Brumpt in the hemocoel of the refractory mosquito Culex pipiens pipiens L. and in that of the susceptible mosquito Aedes aegypti (L.) have been determined. Infected blood, with a high gametocyte count, was injected into the hemocoel of the mosquitoes and the development of the parasites in both hosts was compared with each other and with the natural exogenous cycle. Serial sections of the infected mosquitoes were used in these experiments. It was concluded that (1) the parasites develop at the same rate in the hemocoel of the injected susceptible mosquito as on the stomach wall of the naturally infected host; (2) development of the parasites in the hemocoels of both susceptible and refractory mosquitoes was parallel for the early stages until the 3rd day; (3) oocysts in the refractory host deteriorated and receded from the host tissues after the 4th day; (4) adequate metabolites were available to support development in the resistant host for the first 3 days but undetermined toxic factors were probably responsible for the resultant deterioration and death of the parasites. The relations between the exogenous stages of malaria and the invertebrate host, especially those between the parasite and the tissues, are poorly understood. Each species of Plasmodium finds favorable environments for development only in certain species of mosquitoes, whereas development may be restricted in part or completely suppressed in numerous other species of mosquitoes. The developmental stages of most malaria parasites in susceptible mosquito species have been known in detail since they were first described. We know very little, however, about the extent of development of the exogenous stages in resistant or refractory species of mosquitoes. Little is known about the relationship between extent of development and the innate resistance of such mosquitoes to malaria. One of the earliest investigations in this regard was reported by Huff (1927). He traced the development of Plasmodium cathemerium Hartman in Aedes sollicitans (Walker) which is resistant to the parasite and in Culex pipiens L. which is susceptible, and found that development to the ookinete stage was about equal in both species. He did not find differences in the rates of digestion of the blood meals or in the appearance of the parasites in the stomachs of these mosquitoes, and factors responsible for susReceived for publication 7 June 1968. *This investigation was supported in part by Public Health Service research Grant AI 05253, from the NIAID. c ptibility were not recognized. In 1934 Huff showed that ookinetes of P. cathemerium may form in the stomachs of a resistant strain of C. pipiens but they degenerated and died without penetrating the stomach wall. There had been no attempt to determine the possibility of parasites developing beyond the stomach phases in either refractory or susceptible species until one of us (Weathersby, 1952) injected parasites directly into the hemocoel of the mosquitoes. The stomach wall was thus bypassed. Susceptibility was not altered by this technique since the susceptible mosquitoes became infected and the refractory mosquitoes did not. It was demonstrated (Weathersby, 1952, 1954) that the factors g verning innate susceptibility of mosquitoes to malaria were systemic and not restricted to, or localized in, the stomach wall. In those experiments the progress of the development of the parasites was not observed in detail but susceptibility was evaluated on evidence of subsequent sporozoites in the mosquitoes' salivary glands and on the ability of the mosquitoes to infect susceptible vertebrate hosts. The purpose of this study is to show the daily development of exogenous forms in the hemocoel of refractory mosquitoes, in comparison to the development in the hemocoel of susceptible mosquitoes, and to determine the relations of such development to the innate susceptibility, or more specifically the immunity, of certain mosquitoes to malaria.