The generation of nerve impulses in mammalian axons by changing the concentrations of the normal constituents of extracellular fluid.

1. Experiments have been performed to determine what changes in normal constituents of extracellular fluid are necessary to generate action potentials in mammalian axons. 2. Single and multifibre preparations of rat spinal roots were tested with Krebs solutions in which Na+, K+, Ca2+, Mg2+, pH, PCO2 or osmotic pressure were varied. 3. [Ca2+] below 1.0 mM produced impulses in all preparations. Lowering [Mg2+] did not generate any impulses but did enhance the response to low [Ca2+]. 4. Increasing [Na+] or [K+] caused excitation in some of the multifibres; increased [Na+] evoked 'off' responses in two single fibre preparations. The response to low [Ca2+] was enhanced by increasing [Na+] and depressed by increasing [K+]. 5. Increasing the osmotic pressure (with glucose) did not generate impulses and depressed the response to low [Ca2+]. 6. Changing the pH of Krebs solution did not generate impulses, but modified the response to other stimuli. The response to low [Ca2+] was increased as pH increased from pH 7.4 to 8.2, and decreased with pH in the range pH 7.4‐‐6.2. 7. Altering pCO2 did not have any effect on the responses to low [Ca2+] unless pH also changed.