The nature of dorsal root reflexes (DRRs) and their possible role in peripheral inflammation and the consequent hyperalgesia are reviewed. The history of DRRs and the relationship of DRRs to primary afferent depolarization and presynaptic inhibition in pathways formed by both large and fine afferents are discussed. Emphasis is placed on the mechanisms underlying primary afferent depolarization, including the anatomical arrangement of the synapses involved, how depolarization can result in inhibition by decreasing transmitter release, the role of excitatory amino acids and GABA, the manner in which the equilibrium potential for chloride ions is determined in primary afferent fibers, and forms of presynaptic inhibition that do not utilize GABA(A) receptors. There is then a discussion of neurogenic inflammation, including the role of the release of neuropeptides such as substance P and calcitonin gene-related peptide from sensory nerve endings. Evidence is reviewed that links DRRs to a substantial part of the swelling of the knee joint in acute experimental arthritis and to the flare reaction in the skin following intradermal injection of capsaicin. Possible mechanisms by which the level of DRR activity might be enhanced following inflammation are suggested. The consequences of this increase in DRRs may include exacerbation of hyperalgesia as well as of peripheral inflammation. The conversion of an inhibitory process, presynaptic inhibition, to an excitatory one by DRRs can thus lead to pathological consequences.