Investigations during recent years indicate that many different neuroactive substances are involved in the transmission and modulation of somesthetic information in the central nervous system. This review surveys recent developments within the field of somatosensory neurotransmission, emphasizing immunocytochemical findings. Increasing evidence indicates a widespread role for glutamate as a fast-acting excitatory neurotransmitter at different levels in somatosensory pathways. Several studies have substantiated a role for glutamate as a neurotransmitter in primary afferent neurons and in corticofugal projections, and also indicate a neurotransmitter role for glutamate in ascending somatosensory pathways. Other substances likely to be involved in somatosensory neurotransmission include the neuropeptides. Many different peptides have been detected in primary afferent neurons with unmyelinated or thinly myelinated axons, and are thus likely to be directly involved in primary afferent neurotransmission. Some neurons giving rise to ascending somatosensory pathways, primarily those with cell bodies in the dorsal horn, are also immunoreactive for peptides. Recent investigations have shown that the expression of neuropeptides, both in primary afferent and ascending tract neurons, may change as a result of various kinds of peripheral manipulation. The occurrence of neurotransmitters in intrinsic neurons and neurons providing modulating inputs to somatosensory relay nuclei (the dorsal horn, the lateral cervical nucleus, the dorsal column nuclei and the ventrobasal thalamus) is also reviewed. Neurotransmitters and modulators in such neurons include acetylcholine, monoamines, GABA, glycine, glutamate, and various neuropeptides.