The age-related changes in the distribution of enkephalin-immunoreactive (ENK-IR) nerve fibers in relation to the principal neurons were studied in 23 human sympathetic ganglia from patients aged between 22 and 98 years. There were no age-related changes in the diameter of nerve cells and the packing density of the neurons did not change. There was an age-related decrease in the proportion of neurons innervated by enkephalin-containing fibers. In all age groups the neurons innervated by ENK-IR nerve fibers were larger than those neurons which were not surrounded by ENK-IR nerves. The pigment material in the enkephalin-innervated neurons was non-osmiophilic. The small neurons containing dark neuromelanin type of age pigment were not innervated by ENK-IR nerves. It is speculated that ENK-IR preganglionic nerves play a role in maintaining neuronal integrity of sympathetic neurons.