Early cellular swelling following fluid-percussion brain injury was demonstrated in vivo by means of microdialysis in the rat. When rapid cellular swelling occurs, water moves from the extracellular space (ECS) into the cells and the extracellular concentration of ECS marker which does not move into the cells increases. Cellular swelling was therefore demonstrated in vivo as an increase in the dialysate concentration of 14C-sucrose ([14C-sucrose]d) pre-perfused as an ECS marker. The increase in [14C-sucrose]d occurred concomitantly with an increase in the dialysate concentration of K+ ([K+]d) representing large ionic fluxes. The increases in [K+]d and [14C-sucrose]d were both inhibited by kynurenic acid, a broad spectrum antagonist of excitatory amino acids (EAAs), which was administered through the dialysis probe. These findings suggest that early cellular swelling following traumatic brain injury is a result of ionic fluxes mediated by EAAs.