Hypertensive hypoalgesia may be explained by opioid insensitivity (McCubbin & Bruehl, 1994). Opioid antagonism may therefore be expected to have different effects on hypertensives and normotensives during pain assessment. Following ethics committee approval and in accord with the Declaration of Helsinki, this double-blind placebo-control study examined the effects of the opioid antagonist, naltrexone, on the nociceptive flexion reflex (NFR) threshold (Willer, 1977) and electrocutaneous pain tolerance, in 35 unmedicated hypertensive patients (14 female, 47 ± 14 years; mean ± s.d.) and 28 normotensive controls (16 female, 38 ± 13 years). They completed two 3-h sessions, 48 h apart, which began with ingestion of either 50 mg of naltrexone or placebo. The sural nerve was electrocutaneously stimulated to obtain an NFR threshold using an adaptive staircase procedure (Edwards et al. 2001). Pain tolerance was determined using an ascending method of limits. Sural nerve stimulation intensity was increased in 2 mA steps from 0 until participants rated the stimulation as maximum tolerable pain; they then completed a McGill pain questionnaire (Melzack, 1987). A series of 2 Group × 2 Sex × 2 Tablet ANCOVAs, with age as covariate, were performed. During placebo NFR thresholds were not significantly different between hypertensive (16.1 ± 10.5 mA) and normotensive (14.6 ± 7.6 mA) groups, whereas during naltrexone NFR thresholds were higher (p<0.05) in hypertensives (16.6 ± 10.5 mA) than normotensives (12.5 ± 5.6 mA). Opioid blockade significantly reduced NFR thresholds in normotensives but not hypertensives. During pain tolerance assessment, although stimulus intensity at maximal tolerable pain was higher, albeit not significantly, in hypertensives (29.4 ± 8.2 mA) than normotensives (27.1 ± 9.0 mA), the hypertensives rated this stimulus as less (p<0.05) painful (8.3 ± 4.7 arbitrary units (au)) than normotensives (12.0 ± 7.2 au). However, naltrexone had no significant effect on maximal pain tolerance in either group. The lower pain ratings in hypertensives during the maximal pain tolerance assessment agree with previous observations of hypertensive hypoalgesia. In conclusion, the decrease in NFR thresholds with naltrexone in normotensives but not hypertensives confirms that opioids play a role in dampening nociceptive responding in healthy individuals and suggests that hypertensives are characterised by opioid insensitivity during noxious stimulation.