The content and intra-axonal transport of acetylcholine (ACh) and the ACh-metabolizing enzymes choline-acetyl-transferase (CAT) and ACh-esterase (AChE) in the rat sciatic nerve were studied after various experimental procedures. The procedures involved: (1) spinal cord transection (SCT) at the thoracic level 1 day to 3 weeks prior to experiments, to abolish nerve activity of the lower motor neurons (in the lumbar intumescence-sciatic nerve) from supraspinal centres; (2) physical training for 2 h daily during 2 weeks in a rodent treadmill, to increase nerve activity from supraspinal levels; and (3) the use of selective neurotoxins to cause degeneration of descending bulbospinal monoaminergic (MA) neurons. The results of these studies demonstrate that supraspinal nerve influence can modify the axonal transport of ACh and cholinergic enzymes in the rat sciatic nerve, and that descending monoamine (MA) pathways may, at least to some extent, participate in this modulation of intraneuronal dynamics in the motor neuron. Since it has been shown by many investigators that factors which have a trophic influence on skeletal muscle cells both in vitro and in vivo are present in motor nerves and transported along the axons in a distal direction, we suggest that the synthesis and axonal transport of such factors may also be under control of supraspinal nerve activity. Therefore, it is possible that metabolic changes and dystrophy of muscles occurring in patients with lesions of the 'upper motor neuron-type' may also, in addition to other factors, be dependent on changes in intra-axonal transport of various substances in the lower motor neuron.