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Analysis of the actions of electric currents on excitable membranes has contributed greatly to our biophysical understanding of the initiation and transmission of impulses in nerve and muscle. The use of electrical stimulation in trying to unravel the complex structure and to understand the integrative properties of the central nervous system (CNS), however, raises problems of a different order. This is true of the application of electrical stimuli to mixed populations of axons in peripheral nerves in attempts to discover the central actions of inputs from the different receptive fields, from skin, for example, or muscle or joint. But the most complex problems of all are those raised by the application of electrical stimuli to the CNS itself, whether to try to find out how it works, or to try to relieve a patient's disabilities. We would like to be able to specify, for any particular configuration of external electrodes, which populations of neurones and axons will be excited by virtue of appropriate orientation with respect to lines of current flowing cathodally within the non-isotropic conducting medium of the CNS. We would also like to know the quantities and locations of the brief excitatory and inhibitory synaptic actions, and the longer-term 'modulating' actions, which they exert at nearby and remote areas of the brain and spinal cord. In man, much could be accomplished by attentive neurological examinations, comparing sensory, motor and autonomic functions in the presence and absence of chronic stimulation, and correlating particular physiological effects with alterations of particular symptoms. Such examination would invoke all the technical resources of clinical neurophysiology. Direct evidence of the stimulation of particular spinal pathways and neurones, and of the distribution of remote excitatory and inhibitory effects, could be obtained only by multiple electrical recordings from brain and cord in animal experiments.