Sustained exposure to radiofrequency radiation of millimeter wave (MMW) length produces hyperthermia and subsequent circulatory failure. This study sought to determine whether this phenomenon is altered by chronic pretreatment with the nitric oxide (NO) synthesis inhibitorNω-nitro-L-arginine methyl ester (L-NAME). Rats drank either 1) water, 2) water + L-NAME, or 3) water + L-NAME + L-arginine (at 20 and 50 times the dose of L-NAME) for 14 days. Ketamine-anesthetized rats were exposed to MMW until mean arterial blood pressure (MAP) fell to 75 mmHg, at which point MMW exposure was discontinued. MAP initially increased during exposure in all groups; the pressor response in L-NAME-treated rats was greater than that in water-drinking rats. Subsequently, MAP fell in all groups. The MMW exposure time required to reach MAP = 75 mmHg was significantly reduced in L-NAME-treated rats, although survival times (post-MMW) of L-NAME-treated and control rats were not statistically different. Coadministration of L-arginine abolished the enhanced pressor response produced by L-NAME, but did not completely reverse the shortened MMW exposure time in L-NAME-treated rats. Thus, chronic NO synthesis inhibition with L-NAME reduces the ability of rats to withstand 35 GHz microwave heating, suggesting that NO does not mediate the hypotension produced by this form of hyperthermia.