The effect of inflammation on the excitability and the level of substance P (SP) in cat mechanoreceptive C and Adelta dorsal root ganglion (DRG) neurons were studied in vivo using intracellular recording and immunocytochemical techniques. Following injections of carrageenan (Carg) into the cat hindpaw, the percentage of C neurons exhibiting spontaneous activity increased from 7.2 to 20.7% and the percentage of Adelta neurons increased from 6.9 to 18.6%. In contrast to most cells from normal cats, which fired regularly below 10 Hz, many cells from Carg-treated cats fired at higher frequencies or in bursts. Inflammation (Carg treatment) also depolarized membrane potentials, increased membrane input resistance, caused the disappearance of inward rectifying currents and lowered the mean current thresholds of tibial nerve-evoked responses in DRG neurons. With inflammation, the percentage of C or Adelta neurons responding to low threshold mechanoreceptive stimuli increased (C neurons: normal, 13%; inflamed, 41%; Adelta neurons: normal, 13 %; inflamed, 39 %), while the percentage of C or Adelta neurons responding to high threshold mechanoreceptive stimuli remained unchanged. Some receptive field (RF)-responsive cells were injected with Lucifer Yellow and their SP immunoreactivity was determined. Following Carg treatment, substantially higher percentages of RF-responsive cells were SP positive (C neurons: normal, 35.7%; inflamed, 60%; Adelta neurons: normal, 18.2%; inflamed, 66.7%). These combined increases in the excitability of DRG neurons and SP-containing RF-responsive neurons could lead to sensitization of sensory neurons, thus contributing to the development of hyperalgesia.