Morphologic and morphometric alterations of the sciatic nerve from old Sprague-Dawley rats and of lesioned tibial nerve from young and senescent Sprague-Dawley rats were studied. The possible therapeutical effects of treatment with acetyl-L-carnitine (ALCAR) were also investigated, ALCAR being a compound shown to exert a beneficial pharmacological action on diabetic neuropathies. Nerve sections from animals sacrificed under anesthesia were stained with toluidine blue. In old rats, a 6-month treatment with ALCAR markedly reduced the percentage of myelinated fibers (MF) characterized by age-dependent morphologic alterations (4% in treated rats versus 11% in untreated ones), such as myelin balloons, infolded loops of myelin, myelin reduplication, and ovoids. In the lesioned animals, ALCAR-treatment (15-60 days for young rats and 6-9 months for senescent rats) produced a significant increase versus controls in the density of regenerating myelinated fibers (RMF) at 15 days (young rats) and at 30 days (senescent rats) after crush, as well as an increase in the axon diameter in both young and senescent rats at 60 days after nerve crush. The MF diameter (sheath + axons) was significantly larger in treated senescent rats than in controls at 100 days after nerve crush. In ALCAR-treated rats, both young and senescent, the density of degenerative elements was lower and the RMF ratio (RMF density/RMF density + density of degenerative elements) was higher than that in controls at all detection times.