Neurites were transected from spinal neurons in media with normal (125 microM) or reduced NaCl (sucrose substitution). After 12 h the normal ionic environment (conditioned medium with serum) was restored. A one-factor ANOVA comparison found a significant difference in 48 h survival (P = 0.0001). Survival was highest when NaCl was reduced 50% (74% +/- 19 vs. 22% +/- 19 in normal NaCl). Na(+)- and Cl-mediated deterioration may contribute to both gray and white matter injury in CNS trauma.