Given the importance of alpha2-adrenergic receptors in the regulation of catecholaminergic transmission, we analysed the distribution of immunoreactivity corresponding to the C-subtype of alpha2-adrenergic receptor in central catecholaminergic neurons using double-label immunohistochemistry with antibodies directed against alpha2C-adrenergic receptors and tyrosine hydroxylase. Cells exhibiting both alpha2C-adrenergic receptor and tyrosine hydroxylase immunoreactivity were found in most areas containing catecholaminergic cell groups. However, the percentage of double-labelled cells varied in a region-specific manner. In the medulla, alpha2C-adrenergic receptor immunoreactivity was characteristic of only a minority of cells exhibiting tyrosine hydroxylase immunoreactivity (40-43% in area A1/C1, 27-36% in area A2/C2, 35% in area C3) while a larger percentage of double-labelled cells was observed in the pons (65% in A5, 92% in locus coeruleus, 68% in A7). In the midbrain, alpha2C-adrenergic receptor immunoreactivity was detected in most tyrosine hydroxylase-immunoreactive cells in dopaminergic regions (63% in the retrorubral field, 77-83% in substantia nigra, 67% in ventral tegmental area). These results suggest that alpha2C-adrenergic receptors may act as autoreceptors on some central adrenergic and noradrenergic neurons. In addition, the colocalization of alpha2C-adrenergic receptor and tyrosine hydroxylase immunoreactivity in dopaminergic cell groups suggests that reported effects of alpha2-adrenergic receptor agonists in these areas may be mediated by the C-subtype.