Monoamine systems have been shown to be an important part of an endogenous analgesic system of the central nervous system. Some aspects of the anatomical basis of monoamine modulation of nociceptive input were investigated in these studies. Two sites examined where monoamine systems are known to impinge on the pain transmission system included the grey matter of the somatosensory thalamus and the spinal cord. In particular, the connections of noradrenergic systems with these regions were emphasized. In the ventral posterolateral nucleus of the thalamus the presence of a sparse innervation by both noradrenergic and serotonergic fibers was confirmed by electron microscopy. Boutons containing markers for either serotonin or norepinephrine were observed contacting dendrites and somata in this region. The origins of these projections were determined, by retrograde transport studies, to be primarily in the locus coeruleus and the dorsal raphe. Also examined was noradrenergic innervation of the spinothalamic tract neurons which relay information related to pain from the spinal cord. Some catecholamine boutons were observed to contact spinothalamic neurons directly. These included spinothalamic tract neurons of the wide dynamic range and the high threshold category. The presence of noradrenergic elements in the somatosensory thalamus and, in particular, the direct connection with spinothalamic tract neurons at the level of the spinal cord clearly provides an anatomical substrate for influencing sensory mechanisms related to pain.