The direct application of preservative-free morphine sulfate (1.5%, 1 ml, 19.8 μmol) or fentanyl (0.06%, 1 ml, 1.07 μmol) on the superficial radial or saphenous nerve of cats did not alter the response of single C polymodal nociceptive fibers (PMNs) to noxious radiant heat stimulation of their peripheral receptive fields. Intravenous administration of fentanyl (100 or 200 μg/kg, 0.179 or 0.358 μmol/kg) also showed a similar lack of effect on the radiant heat evoked responses of single PMNs. Slight changes in the mean latencies following drug administration were recognized, which were not statistically significant. The use of morphine (1.5%, 1 ml, 19.8 μmol) with preservatives (chlorbutanol 0.5% and sodium bisulfite less than 0.1%) caused conduction block of PMNs within 6–15 min. Subsequent washout of the drug resulted in the return of the unitary discharges within 8 min. Lidocaine (0.25 and 0.5%, 10.7 μmol and 21.4 μmol) caused conduction block within 5–18 min. These data support the classically held concept that opiates, in clinically useful concentrations, do not alter peripheral nerve function.