In common with polymyxins B and E, polymyxin A has now been shown to be composite, separable by counter-current distribution into two components, polymyxin ^41 and polymyxin A2. From the sequential analysis of the fragments obtained by partial acid hydrolysis and enzyme degradation, the structures of these two antibiotics have been determined and, as the formula shows, conform to the basic pattern. In contrast to the polymyxins B and E the polymyxins A have two D-amino-acids, which may account for the high degree of nephro-toxicity. It will be recalled that two D-amino-acids, D-serine and D-leueine, also occur in polymyxin D, the other nephrotoxic antibiotic of this group. Table 1Polymyxin Bl Polymyxin B2 Polymyxin El (= colistin^) Polymyxin E2(= colistin B) Circulin A Polymyxin Al Polymyxin A2 AMOA IOA MOA IOAMOA MOA IOA DAB DAB DABDAB DAB D-DAB D-DABD-Phe D-Phe D-Leu D-LeuD-Leu D-Leu D-Leu Leu Leu LeuLeu lieu Thr ThrMOA is (+)-6-methyloctanoic acid, and IOA is isooctanoic acid. Polymyxin M, isolated by Khokhlov6 in 1956, has now similarly been shown to be a mixture of antibiotics, giving, on hydrolysis, the same aliphatic acids, (+)-6-methyl-octanoic acid and isooctanoic acid, found in the other polymyxins. The amino-acid composition, electrophoretic and chromatographic behaviours, optical rotation and nephrotoxicity of polymyxin M so parallel those of polymyxin A that there can be little doubt that these two antibiotics are identical.