Among the most fascinating riddles in neuroscience is the one concerning the poor regeneration capacity of the adult mammalian CNS. A central aetiological hypothesis for the lack of axonal regeneration in the CNS concerns the inhibitory role of myelin components of the white matter. The main exponent of this hypothesis in the 1980s and 1990s has been Martin Schwab, although before him Martin Berry and others had suggested an inhibitory role for CNS myelin. However, a hypothesis for a negative neurotropic action exerted by CNS white matter was formulated by Lugaro already in 1906. This article is a belated tribute to Lugaro's original contribution in the field of neuroregeneration.