The ease with which Plasmodium falciparum parasites adapt to culture by the method of Trager-Jensen is variable. The strain characteristics of the first three isolates we cultured differed markedly, depending on the ease of adaptation. The West African I, which was cultured readily, proved to be sensitive to all antimalarials assessed by an in-vitro method, caused benign infections in Aotus monkeys, and produced gametocytes both in the cultures and in Aotus monkeys. In contrast, parasites of the Liberian I and Haitian I strains, both of which required an adaptive period of a month or longer proved more tolerant to chloroquine, quinine, and cycloguanil but sensitive to pyrimethamine; commonly produced fatal infections in Aotus monkeys, and did not produce demonstrable gametocytemia. That the differences may be due to the selection of a more virulent and drug tolerant subpopulation is suspected. The implication of these findings, particularly as it may apply to the epidemiology of chloroquine resistant falciparum malaria, is discussed.