We studied the effect of brain and spinal cord injury induced by fluid-percussion on the local synthesis of neurosteroids as measured by a gas-chromatographic/mass-spectrometric method. In the nervous system of sham operated rats i.v. infusion of pregnenolone (PREGN)-sulfate results in a 2-4 fold increase in PREGN, progesterone (PROG), 5alpha-dehydroprogesterone (5 alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one (3 alpha 5 alpha-THP, allopregnanolone) concentrations, as compared to vehicle treated rats. When PREGN-sulfate was infused 1,3 or 7 days after brain or spinal cord injury it was observed a large time-dependent increase of FROG, 5 alpha-DHP and 3 alpha 5 alpha-THP levels in the peri-focal but not in the focal site. This increase in neurosteroids content may be due essentially to the glial cells hyperplasia in the peri-focal area and to an activation of the pathways involved in the metabolism of PREGN-sulfate to FROG, 5 alpha-DHP and 3 alpha 5 alpha-THP. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.