Cation-chloride co-transporters (CCTs), particularly NKCC1, may be important in epileptogenesis. We have performed a detailed histological examination of NKCC1 in large samples of patients with hippocampal sclerosis (HS) or focal cortical dysplasia (FCD), pathologies both commonly associated with pharmacoresistant epilepsy. We consistently found increased immunoreactivity for NKCC1 in HS and FCD, but not in adjacent histologically normal cortex. Our results suggest that NKCC1 might contribute to the pathogenesis or pathophysiology of HS and FCD, thereby potentially offering a new therapeutic target in the treatment of pharmacoresistant epilepsy.