Catecholaminergic axonal varicosities identified by immunocytochemical staining for dopamine-beta-hydroxylase were observed at the light microscopic level apposing the somata of retrogradely labeled spinothalamic tract neurons in the monkey spinal cord. Three retrogradely labeled and two intracellularly labeled spinothalamic neurons were serially sectioned and examined at selected intervals at the electron microscopic level. Electron microscopic study revealed that axonal boutons directly contacted the somata and/or dendrites of lamina I, IV, and V spinothalamic tract neurons. All of the profiles apposing one of the retrogradely labeled lamina I spinothalamic tract neurons were categorized from eight planes of section spaced at 1-micron intervals. Of the 305 profiles counted that were adjacent to this soma, 17 (5.6%) stained positively for dopamine-beta-hydroxylase. Of these 17 appositions, three were followed in serial sections to confirm that they had synaptic thickenings and alignment of vesicles along the membrane contacting the spinothalamic tract soma. Catecholaminergic boutons were observed apposing the somata and dendrites of intracellularly filled STT cells characterized as high threshold and wide dynamic range neurons. These observations clearly indicate a direct innervation of spinothalamic tract neurons by catecholaminergic neurons, providing anatomical data to support previous physiological findings demonstrating that catecholamines modulate nociceptive transmission.