This study investigated the occurrence and levels of neurotoxic contamination in UK estuaries by the determination of cholinesterase (ChE) activity in the muscle of the flounder (Platichthys flesus). Samples were obtained from 16 sites in the estuaries of the rivers Humber, Mersey, Tamar, Tees and Tyne. ChE activity levels were compared to those at a reference site- the River Alde, Suffolk. Twelve sites exhibited significantly (p<0.05) reduced ChE activity. The Tyne estuary showed a strong gradient of effect that suggested a source of neurotoxic-contamination upstream of the sampled sites. Representative water samples from several of the estuaries were analysed for the presence of 32 organophosphate (OP) and 20 carbamate (C) pesticides from which residues of nine OPs and six Cs were detected. Correlation analysis of ChE activity with gender, size, GSI, HSI and condition factor suggested that these variables did not influence neural activity in this study. It was concluded that the reduction in ChE activity was contaminant mediated and that OP and C pesticides were probable contributors. Influences on ChE activity, higher order implications and its use as a monitoring tool, including reactivation techniques, are discussed.