The endoplasmic reticulum (ER) is the main site of secretory protein production and folding and its homeostasis under environmental stress is vital for the maintenance of the protein secretory pathway. The loss of homeostasis and accumulation of unfolded proteins in the ER is referred to as ER stress. Although, gamma-aminobutyric acid (GABA) is an important regulator of stress response in plants, its roles during ER stress remains unclear. This study investigated the involvement of GABA in the ER stress response of plants. For this, changes in GABA metabolism under ER stress was analysed in Arabidopsis thaliana, then to study the response of the ER-folding machinery, plants were treated with exogenous GABA under ER stress. The antibiotic tunicamycin, which inhibits N-glycosylation was used to specifically induce ER stress. This stress up-regulated the expression of five glutamate decarboxylase (GAD) genes except GAD2 and GABA content of A. thaliana plants increased with an increasing concentration of tunicamycin (0.1 mu g ml(-1) and 0.25 mu g ml(-1)). Moreover, expressions of genes involved in the conversion of GABA to succinate was also induced, while genes involved in transport across plasma and mitochondrial membrane showed no response to ER stress. The exogenous treatment of plants with 1- and 5mM GABA increased plant performance under ER stress but 0.1 mM proved ineffective. Plants treated with GABA under ER stress had decreased expression of ER stress marker genes such as BIP1, BIP3 or CNX, but the expression of genes related to ER stress perception or ER-associated protein degradation showed no changes with respect to GABA treatments.