1. The actions of three saxitoxin (STX) analogues have been studied on the frog sartorius muscle fibre and the squid giant axon. One‐‐neosaxitoxin‐‐is a natural analogue, and two‐‐decarbamylsaxitoxin and reduced saxitoxin‐‐are synthetic. 2. The maximum dV/dt of the action potential in paired‐muscle protocol is reduced by the analogues with relative potencies: STX (1), tetrodotoxin (1), neo‐STX (1), decarbamyl‐STX (0.2) and reduced‐STX (0.01). 3. In constant‐current studies on frog muscle fibres and in voltage‐clamp studies on squid axons, all three analogues block only the sodium channel without affecting the potassium channel. 4. All three analogues bind to the same site as does STX in a competitive manner. 5. The experimental results suggest that the active groups in STX are the 7,8,9 guanidinium and the C‐12 hydroxy groups. The carbamyl group contributes to, but is not essential for activity. 6. Stereospecific groups in the tetrodotoxin (TTX) molecule are the 1,2,3 guanidinium and the C‐9, C‐10 hydroxy groups. C‐4 and C‐8 groups are also important. 7. As new view is proposed in which STX and TTX can bind to a receptor located in the outside surface of the membrane very close to the orifice of the sodium channel.