Experimental and clinical studies in animals and humans have indicated that nociceptive nerve fibres can acquire sensitivity to norepinephrine after injury or chemical sensitization. To evaluate the functional relevance of such sensitization, we recorded the activity of single polymodal C-fibre afferents in healthy human volunteers and investigated whether intense physiological sympatho-excitation could affect their firing properties. This was studied before and after chemical sensitization of receptive fields by topical application of mustard oil. All afferent C fibres investigated (11 units in 10 subjects) were mechano-heat-sensitive, and four of seven fibres subjected to mustard oil were also chemosensitive. Putative sensitivity to sympathetic stimulation was investigated during low-frequency (0.25 Hz) electrical stimulation of the unit receptive field at a threshold intensity sufficient to evoke an action potential in the afferent fibre after every second to third stimulus. Following a prolonged period of silent rest, sympathoexcitation was elicited by forced mental arithmetic for 60 s, again followed by a long silent rest period. During stress, sympathetic nerve traffic increased to 625 +/- 146% of the control level, while firing of the afferent units remained unchanged. There was no sign of sympathetically mediated direct activation of afferent units and no change in the relative amounts of afferent activations caused by the background electrical stimulation. Results were similar for all units, both before (seven units in six subjects) and after (seven units in seven subjects) chemical sensitization of their cutaneous receptive field. The results suggest that if chemical sensitization of nociceptive C afferent neurons with mustard oil does induce sensitivity to noradrenaline in humans, it is not sufficient to make C nociceptive fibres respond to short-lasting physiological variations in sympathetic outflow.