The effects of clonidine on the activity of single substantia nigra dopamine neurons were studied in the chloral hydrate anesthetized rat. Although clonidine did not affect the firing rate of the cells, it regularized the firing pattern and decreased burst firing at 2-8 micrograms kg-1 i.v. These effects were antagonized by the alpha 2-antagonist yohimbine. Yohimbine (1.0 mg kg-1) deregularized the firing pattern and increased the firing rate as well as the burst firing. The regularization produced by clonidine is discussed in terms of synaptic efficacy. The results might explain the therapeutic effects of clonidine in certain neuropsychiatric disorders.