In vitro studies concerned: a) the lowest conc. of sulfadiazine causing bacterio-stasis of Flexner, Sonne, Schmitz, and Shiga strains of Shigella in 1% tryptone broth, using approx. 100 organisms as inoculum; and b) a comparison of the bacteriostatic effect of 8 sulfonamides against the same 4 spp. of Shigella using identical series of dilutions of the drugs, and using sulfathiazole, the most active drug, as the standard against which comparisons were made. Results showed Flexner strains to be most sensitive to the action of the drugs and Sonne most resistant. Sulfapyrazine required 1.8 times as much as sulfathiazole to achieve the same effect, and sulfaguanidine 60 times. Other sulfonamides showed values between these. Total and dissolved sulfonamide detns. on soft stools of patients treated by the oral administration of various of the sulfonamides were made and the levels in blood were compared. The Bratton and Marshall procedure, slightly modified when used on stools, was used. Fecal levels were 2-8 times higher than blood levels for the absorbable drugs. Differences were wider with the poorly absorbable compounds. A weighting of the blood and fecal values based upon the comparative efficacy of inhibition by the various drugs in vitro showed sulfapyrazine, sulfathiazole, sulfadiazine, and sulfamerazine to be present in the blood in amts. considered efficacious. Judgment based on these and efficacious fecal levels, and the comparison between these pharmacological findings and clinical and bacteriological observations on the patients results in the recommendation of sulfapyrazine and sulfadiazine as the drugs of choice, with sulfasuxidine indicated when a poorly absorbable compound is desired. A dose of 4 gm. daily of sulfapyrazine or sulfadiazine for 7 days by mouth is recommended for adults. Intraven. administration of the Na salt may be used to initiate treatment in those individuals with troublesome vomiting, but is not recommended as a regular procedure because fecal levels are not built up as high by this route. Directions for the prophylactic use of sulfonamides in Flexner and Schmitz outbreaks are also given. Attention is called to the existence of cases due to resistant forms of the various spp. and appropriate care is cautioned in treating such cases.