Projections from the locus coeruleus (LC) to the centrolateral thalamus (Cl) and the medial prefrontal cortex (PfCx) were studied using orthodromic and antidromic stimulation techniques. The LC is a major noradrenergic source in the central nervous system, and its descending projections provide an important source of pain suppression at spinal level. Previously, the author has described a cortico-thalamic loop involved in pain modulation. The present paper reports on a study of the participation of LC as part of an ascending pain-control system acting on the cortico-thalamic loop.Rats were anaesthetized with halothane, and single unit recordings were made in LC using glass micropipettes. Stainless steel electrodes were placed in cortex and thalamus for electrical stimulation.Stimulation in PfCx or Cl produces antidromic responses in neurons in LC. The latencies, conduction velocity and location of neurons in LC projecting to PfCx or Cl structures are described. Separate projections to both structures have significantly different conducting velocities, arriving earlier at Cl (mean conduction velocities 0.27 and standard deviation +/-0.06 m/s) and then at PfCx (mean conduction velocities 0.20+/- 0.04 m/s). The presence of orthodromic responses suggests reciprocal connections. The paper also describes the suppression of spontaneous and nociceptive-evoked activity in the PfCx and Cl following electrical stimulation in LC.It is proposed that the LC innervation could be associated with an ascending noradrenergic system acting upon a Cl-PfCx pain-modulation mechanism. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.