The olive oil phenolic oleocanthal is a natural nonsteroidal anti-inflammatory compound that irritates the oral pharynx in a dose-dependent manner. It has been proposed that the biological activity of oleocanthal is partially responsible for the beneficial health effects of the Mediterranean diet. Virgin olive oil containing oleocanthal is often added as an ingredient in a number of cooked dishes, and therefore it is of great importance to understand how best to preserve the putative health-promoting benefits of this compound, as olive oil phenolics are subject to degradation upon heating in general. One extra virgin olive oil containing 53.9 mg/kg oleocanthal was heated at various temperatures (100, 170, and 240 degrees C) for set time periods (0, 1, 5, 20, 60, and 90 min). Oleocanthal concentrations were quantified using HPLC, and its biological activity was determined with a taste bioassay measuring the intensity of throat irritation. Results demonstrated that oleocanthal was heat stable compared with other olive oil phenolics, with a maximum loss of 16% as determined by HPLC analysis. However, there was a significant decrease of up to 31% (p < 0.05) in the biological activity of oleocanthal as determined by the taste bioassay. Although there was minimal degradation of oleocanthal concentration, there was a significant decrease in the biological activity of oleocanthal upon extended heating time, indicating a possible loss of the putative health -benefiting properties of oleocanthal. Alternatively, the difference in the concentration and biological activity of oleocanthal after heat treatment could be a result of an oleocanthal antagonist forming, decreasing or masking the biological activity of oleocanthal.