In the present report 1646 persons were under observation to determine whether or not a suitable method of drug prophylaxis was available for use in a highly malarious section of Georgia and Florida. In the area where these studies were conducted mosquito control measures were objectionable and in many cases impossible due to the topography. Initial blood smears in the first area indicated a blood parasite index of 16.9 per cent. This has been reduced to 0.3 per cent over a period of two years. Atabrine proved to be the most successful prophylactic agent, although quinine seemed to exert a helpful influence in reducing the malarial incidence. The cooperation of patients taking quinine was difficult to obtain and in a few cases it was necessary to discontinue medication because of idiosyncrasies and toxic reactions. No toxic reactions to Atabrine were observed. After the administration of both Atabrine and Plasmochin to persons residing in the prophylactic areas, the number of malarial carriers and cases exhibiting both gametocytes and schizonts was materially reduced. Due to the natural variations of malarial intensities caused by fluctuations in climatic conditions these prophylactic experiments should always be continued over a period of several years to furnish the maximum amount of reliable information.