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Abstract: Ethnopharmacological relevance: The Q’eqchi’ Maya possess a large selection of plants to treat neurological disorders, including epilepsy and susto (fright), a culture-bound illness related to anxiety disorders. Aim of the study: To investigate the activity of antiepileptic and anxiolytic plants in the GABAergic system, and determine if there is a pharmacological basis for plant selection. Materials and methods: Ethanol extracts of 34 plants were tested in vitro for their ability to inhibit GABA-transaminase (GABA-T) or bind to the GABAA-benzodiazepine (BZD) receptor, two principal drug targets in epilepsy and anxiety. Pharmacological activity was correlated with relative frequency of use, based on informant consensus. Results: Ten plants showed greater than 50% GABA-T inhibition at 1mg/ml, while 23 showed greater than 50% binding to the GABAA-BZD receptor at 250μg/ml. Piperaceae, Adiantaceae and Acanthaceae families were highly represented and active in both assays. There was a significant positive correlation between GABA-T inhibition and relative frequency of use for epilepsy, and an even stronger correlation between GABAA binding and relative frequency of use for susto (fright). Conclusions: Clearly, Q’eqchi’ traditional knowledge of antiepileptic and anxiolytic plants is associated with the use of pharmacologically active plants. Based on the evidence, it is suggested that the mechanism of action for some traditionally used plants may be mediated through the GABAergic system. [Copyright &y& Elsevier]