Activation of thin fibre muscle afferent nerves by metabolic by-products plays a critical role in the initiation and maintenance of the autonomic response to exercise and the metabolic profile of active muscle can influence the response. The purpose of this report was to determine responsiveness of sensory neurones innervating muscles comprised predominately of the glycolytic and oxidative fibres to protons and capsaicin using whole cell patch clamp methods. Dorsal root ganglion (DRG) neurones from 4-6 weeks old rats were labelled by injecting the fluorescence tracers (1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine percholate) in the muscle 3-5 days prior to the recording experiments. The percentage of the DRG neurones innervating glycolytic and oxidative muscle was similar in response to both protons and capsaicin. However, the neurones innervating glycolytic muscle had greater inward current amplitude responses to protons and capsaicin as compared with oxidative muscle. The peak current amplitudes to pH 6.0 were 0.84±0.06 nA (oxidative muscle) vs. 1.36±0.07 nA (glycolytic muscle, P<0.05). The capsaicin-induced current amplitudes were 2.3±0.15 nA (oxidative muscle) vs. 3.1±0.21 nA (glycolytic muscle, P<0.05). 88% of neurones that responded to pH 6.0 with a sustained current also responded to capsaicin. Capsaicin exposure enhanced the proton responsiveness in the neurones innervating the muscle; and protons also increased the capsaicin response. These data suggest that 1) receptors mediating protons and capsaicin responses coexist in the DRG neurones innervating muscle; 2) the responsiveness of acidosis and capsaicin can be sensitized by each other; and 3) DRG neurones with nerve endings in a glycolytic muscle developed greater inward current responses to protons and capsaicin than did those with nerve endings in an oxidative muscle.