The observation that Parkinson's disease (PD) is associated with locus coeruleus (LC) noradrenergic neuronal degeneration suggests that the LC noradrenergic system may be involved in the pathogenesis and natural progression of the destruction of the substantia nigra (SN) dopaminergic neurons in Parkinson's disease. The relationship of these two systems was examined by injection of subtoxic doses of MPTP into unilateral LC 6-hydroxydopamine (6-OHDA) lesioned mice. A significant loss of dopaminergic cells was only found in the SN on the side of the LC lesions. These results suggest that the LC may have protective effects on SN dopaminergic neurons.