With the expansion of agricultural areas within the Mekong River Delta in Vietnam, a concurrent, dramatic increase has occurred in agrochemical usage. To date, little consideration has been given to the negative impacts of this agricultural activity on the aquatic resources of the region. Both acute toxicity and subacute effects on brain cholinesterase (ChE) of two of the most commonly used insecticides, diazinon and fenobucarb, on adult native snakehead (Channa striata) were evaluated in a static, nonrenewable system, the environmental parameters of which, such as dissolved oxygen, water temperature, and pH, fluctuated similarly to field conditions. Four levels of insecticides, from 0.008 to 0.52 mg/L (for diazinon) and from 0.11 to 9.35 mg/L (for fenobucarb), were tested to assess the effects on the brain ChE activity of the snakehead up to 30 and 10 d for diazinon and fenobucarb, respectively. Diazinon was highly toxic to this fish species, with a 96-h median lethal concentration (LC50) of only 0.79 mg/L, and it also caused long-term ChE inhibition, with activity still significantly inhibited by 30% after 30 d for the three highest concentrations. Fenobucarb was less toxic to this species, with a 96-h LC50 of 11.4 mg/L. Fenobucarb caused more rapid ChE inhibition but also rapid recovery. The results of the present study indicate an urgent need to regulate the usage of these pesticides in the Mekong River Delta.