Exogenous [gamma]-aminobutyric acid (GABA) and GABA agonists attenuate nociceptive behaviors in animals and decrease excitability and conduction in somatic and vagal nerves. The present exploratory study examines the effects of GABA on the responses of 38 single primary afferent sural and plantar fibers to electrical, mechanical, chemical, and thermal stimulation. Numerous stimulus techniques were developed, implemented, and tested to establish the validity, reliability, and suitability for use on the mouse skin-nerve ex vivo preparation. A major finding was that a 980 nm infrared diode laser proved very suitable for evoking repeatable graded responses from heat-responsive C fibers and for the study of GABA effects. None of 7 low threshold mechanoreceptors and cooling thermoreceptors had a change in response properties in the presence of GABA. All fibers sensitive to noxious heat and protons were also sensitive to strong mechanical stimuli and were presumed nociceptive. During repetitive activation by electrical stimulation of the nerve, 3 of 6 C fibers had a continued progression of conduction velocity slowing in the presence of GABA. During mechanical stimulation, GABA suppressed the responsiveness of 5 of 17 C and A[delta] fibers. During noxious heat or proton stimulation, 4 of 7 heat-sensitive and 1 of 1 proton-sensitive C fibers had suppressed responsiveness in the presence of GABA. GABA-induced changes in the responses of nociceptors to noxious stimulation are in agreement with animal behavior studies and lend support to the further investigation of GABA and GABA agonists as peripheral analgesics.