To determine whether exposure to radiofrequency radiation (RFR) would induce sufficient thermal stress to activate endogenous opioid mechanisms, male Swiss Webster mice were exposed to 10, 15, and 20 mW/cm2 RFR in a 2450-MHz waveguide system for 10 min at specific absorption rates (SARs) of 23.7, 34.6, and 45.5 W/kg, respectively, then tested in the abdominal constriction paradigm. Confinement in the RFR exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that was not blocked by naltrexone. Exposure of confined mice to RFR raised body temperature and further increased analgesia in an SAR-dependent manner. The high SAR-induced analgesia, but not the hyperthermia, was blocked by naltrexone. These findings suggest that 1) RFR produces SAR-dependent hyperthermia and analgesia, and 2) RFR-induced analgesia is mediated by opioid mechanisms while confinement-induced analgesia involves nonopioid mechanisms.