Summary 1. Ten antibiotics have been studied in vitro by Hansen and Bradin et al., and among these agents, only antibiotic “S” and NA7M10 appear to act against E. histolytica, and not indirectly by inhibition of associated bacteria. 2. Thirty-one naturally infected macaques were given orally maximum tolerated amounts of antibiotic “S”, aureomycin, actidione, lupulon, subtilin, and a mixture of bacitracin, polymyxin B and streptomycin, as well as NA7M10 subcutaneously. 3. Aureomycin, in amounts which were eventually lethal, provided temporary clearance of amebas for periods up to 25 days. The mixture of three antibiotics, (bacitracin, polymyxin B and streptomycin), provided immediate cessation of diarrhea, prompt gain in weight and at least temporary clearance of E. histolytica in three of six monkeys given tolerated amounts. 4. Antibiotic NA7M10, while most active in vitro (at 1:5 million dilution) proved to be lethal on subcutaneous injection in four of eight animals when given in doses of 8 mgm. per kilo or more. Lower doses given over 7 days, cleared 2 of 4 macaques of E. histolytica for periods up to 30 days after therapy. 5. The advantage of the tri-antibiotic mixture, as a possible substitute for emetine, is that it may afford prompt symptomatic relief of diarrhea or dysentery in tolerated dosage. NA7M10 deserves consideration, provided a suitable form for oral use is made available. 6. The necessity for interpretation of these results, except with aureomycin and NA7M10, as “contact” antibiotic therapy without appreciable systemic effects is emphasized. 7. Should these studies be pursued in man, it is imperative that a systemically active amebacide be employed subsequently.