The occasion of the presentation of the eighth Gordon Holmes Lecture left me feeling both honoured and awed, as a result of my review of the Selected Papers of Gordon Holmes (Phillips CG: Selected Papers of Gordon Holmes, compiled and edited for the Guarantors of Brain. Oxford University Press, 1979), kindly presented to me by the sponsors of the meeting. This volume lists 174 publications produced over a 55-year period, and contains reprints of contributions to neuroanatomy, neuropathology, and to disorders that affected the adrenal cortex, the spinal cord, the cerebellum and the cerebral cortex. Yet I also feel a sense of sadness; the invitation to present the lecture came from the late Anita Harding who, such a short time before her illness, gave me personal guidance and encouragement. In this lecture I endeavour to follow the example of Gordon Holmes, namely the stepwise analysis of a clinical problem, first by observation of the patient, followed by the application of techniques that can clarify it, leading to new knowledge not only about the specific disorder, but also about the nervous system and human biology in general and, it is to be hoped, to more effective therapy.