When released in peripheral tissue, ATP causes pain by activating P2X receptors. Using skin-n.saphenous preparation we investigated the action of the P2 agonist on single nerve fibre activity and possible coupling of opioid and P2X receptors. Altogether the effects of ATP (1 mM) were tested in 74 fibres, 30 of them (40%) were excited by ATP: the mean discharge frequency was 0.05±0.002 Hz in the control and 0.28±0.08 Hz after ATP application (p<0.001). It must be noted that ATP have excitatory effect predominantly on C-fibres 18 from 25 (72%). By the contrast only 9 from 34 (26 %) of A[delta] and 3 from 15 (20 %) of Ab-fibres were excited by ATP. After that we used leu-enkephaline (5 mM) as a selective agonist of m- and [delta]- opioid receptors. We found that in 23 from 26 ATP sensitive fibres Leu suppressed ATP induced activation. The action of Leu was substantially reversed by naloxone (10 mM) in 15 tested fibres. In a special trial we found that the response to a selective agoniste of P2X receptors: a,b-methylene-ATP (1 mM) is also inhibited by Leu in a naloxone-dependent manner (n=3). a,b-methylene-ATP increased the discharge frequency of these fibres by a factor of 3.2±0.5, Leu (5 mM) attenuated this excitation by a factor of 1.8±0.4, while naloxone (10 mM) reversed this inhibition for 30–40%. Here we show that P2X receptors from the peripheral nociceptors is under partial, although considerable control by opioid receptors and are functionally coupled in the nerve fibres.