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1. Certain aromatic polysulphonic acids, previously tested for inhibition of the haemolytic activity of staphylococcal alpha-toxin, together with some additional related compounds, were tested as possible inhibitors of alpha-toxin in mice. 2. Compounds that inhibited the haemolytic activity of alpha-toxin at concentrations of 0.16mm or less [compounds (I), (II), (IV), (V), (VII) and (VIII)] were found to inhibit the lethal effect of alpha-toxin. 3. With the exception of compound (VIII), amounts of 1mg. were required to inhibit 4 LD(50) of toxin when the test compounds were premixed with alpha-toxin before injection; comparable inhibition with 0.3mg. of compound (VIII) was achieved without prolonged premixing. 4. Mixtures of alpha-toxin and compounds (I) and (II) containing an excess of test compound showed markedly diminished inhibitory activities. 5. The ;half-molecule' analogues of group 1 [compounds (III) and (XVIII)] were non-inhibitory. 6. Compounds (I)-(V), when administered separately from alpha-toxin by the same route (intraperitoneal), were active only when injected almost simultaneously with toxin, whereas compounds (VII) and (VIII) were strikingly inhibitory when injected 15min. before or after the toxin. 7. Compound (VIII) failed to inhibit the lethal effect of alpha-toxin when injected by a different route (intravenous).

1. The effect of a number of aromatic polysulphonic acids on the kinetics of haemolysis of rabbit erythrocyte suspensions by crude staphylococcal alpha-toxin was studied at pH8.6 and 6.8. 2. All of the inhibitory compounds caused an increase in the prelytic lag time (tau) of the sigmoid haemolysis curves, an increase in the time to reach 50% haemolysis (t((1/2))) and a decrease in the maximum rate of haemolysis (R(max.)). The most inhibitory compounds caused a 50% decrease in R(max.) at concentrations between 0.1 and 0.2mm. 3. The effect of pH varied considerably: compounds (I) and (II) were almost equally inhibitory at both pH values, compounds (IV) and (IX) were more inhibitory at pH6.8 than at pH8.6, and compounds (VII), (VIII), (X), (XI) and (XII) were more inhibitory at pH8.6. 4. Increased time of premixing alpha-toxin with compound (I) caused increased inhibition. 5. An attempt was made, where possible, to relate the inhibitory activity to the structure of the test compound.