On the premises of clinical studies, a possible contribution of oxygen radicals has been considered to the development of inflammatory pain and hyperalgesia. In a rat skin-saphenous nerve preparation using standard teased-fiber techniques (n = 57) hydrogen peroxide (1 mM, 10 mM and 50 mM) was applied in aqueous solution to cutaneous nerve endings of unmyelinated nociceptive afferents. Superoxide anion and hydroxyl radical were secondarily generated as reaction products from pyrogallol (1 and 10 mM) and from Fe-EDTA (1 mM) in hydrogen peroxide, respectively. None of these substances, except exceptionally, induced ongoing activity nor nociceptor sensitization to heat and mechanical stimuli. If occasionally there was a weak excitatory effect, the fibers were left with a profound desensitization to adequate stimulation. The addition of hydrogen peroxide did not enhance sustained responses to solutions of high proton concentration (pH 6.1). Responses to combined inflammatory mediators (bradykinin, serotonin, histamine and prostaglandin E2, 10 microM) were increased, on average, when hydrogen peroxide was added but this effect did just not reach significance. These findings suggest that oxygen radicals do not play a major and specific role in nociceptor sensitization.