Until such time as the erythrocytic stages of Plasmodia can be grown axenically in a defined medium, the correct interpretation of the results of experiments carried out with parasites developing intracellularly or maintained separated from their host red cells must remain in question. There can be no doubt therefore that for a basic understanding of the parasite it must be cultivated free of the red cell, in a defined medium, obtained in relatively high yield and capable of continued passage in culture. Now it is clearly understood, as Dr. Trager has emphasized, that this optimal state has not been reached but his work encourages optimism and as he says, “This situation could change radically as new information is obtained.” In this discussion I should like to deal with: 1) environmental and nutritional requirements; 2) the metabolism of the parasites and their survival, considering the possible short biological half-lives of the high energy constituents of the medium; 3) the importance of a balance of medium constituents and the determining of intracellular specificity; 4) the CoA requirement; and 5) the susceptibility of certain host cells in determining intercellular specificity.