To search for the sequential compromise of the spinal cord, nerves, and skeletal muscle in mice chronically infected with Trypanosoma cruzi, animals were subjected to electromyographic investigation, end-plate recordings, and histological studies at 7, 15, 37, 60, 90, 120, 180, 270, and 360 days postinfection. Electromyographic studies showed signs of motor unit remodeling as early as 15 days postinfection, when diminished duration and amplitude of motor unit potentials pointing to a primary muscle involvement were found. Thereafter, certain features of denervation, reinnervation, and primary muscle involvement were often found to coexist. Low miniature end-plate potentials with normal frequency and acetylcholine quantum content were found in end-plate recordings made at the phrenic-diaphragm in vitro. Double end-plate potentials were observed in most of the tested muscle fibers from day 90 postinfection. All these features suggest post-synaptic damage of the end-plate and the presence of reinnervation after day 90 postinfection. Histological studies disclosed inflammatory infiltrates consisting of lymphocytes and macrophages, with vasculitis as the main lesion in the hamstring muscles; intracellular parasites were seen in 25% of the cases. Neuropathic features, as expressed by type fiber grouping and grouped muscle fiber atrophy, were found. On nerve examination epineural, perineural, and endoneural vasculitis were seen. Digestion chambers and myelin ovoids (axonal degeneration) were observed. In teased fiber preparations, segmental internodal and paranodal demyelination and remyelination were found. The lumbar inflammatory spinal cord failed to show grey or white matter infiltrates. However, spinal roots and dorsal root ganglia were densely affected by inflammatory cells.