The human substantia nigra can react to destruction of the basal ganglia in several ways. In ten brains with massive unilateral infarction of the basal ganglia slight to moderate nerve cell loss was present in the ipsilateral substantia nigra. The severe nerve cell loss reported in mostly young experimental animals was not observed. One case also displayed a fine network of myelinated and unmyelinated fibers surrounding pigmented nerve cells and dendrites in the ispilateral substantia nigra. Electron microscopy of the substantia nigra from this case showed neurofilamentous hyperplasia, paired helical filaments and rare straight filaments, but only on the side ipsilateral to the striatal infarct. The nerve cell loss in the ten cases was interpreted as a mainly retrograde degeneration, the perineuronal sprouts in case 10 as a reaction to partial deafferentation, and the paired helical filaments as either a retrograde or a transsynaptic reaction in the substantia nigra ipsilateral to the basal ganglia destruction.