Spontaneous blink rates are controlled by a definable neural system originating in PPRF with facilitatory modulation from SN and superior colliculus and inhibitory modulation provided by cerebellum and occipital cortex. The thalamus may also be involved but the result of its influence is not clear. Reflex blinking is often reduced when spontaneous blink rate is increased and the reverse applies as well. The anatomic control of reflex is primarily in structures in the caudal half of pontine tegmentum and rostral midbrain. However, SN and cerebellum and other structures that regulate blink rate also modulate reflex blinking. Neurochemical control as determined by neuropharmacological experiments is exerted by dopaminergic, cholinergic and GABAergic systems of brain stem. Dopamine activity correlates directly with blink rate whereas agonism of the other two relevant neurotransmitter systems may inhibit blink rate. Clinical implications in central nervous system disease are currently restricted to Parkinson's disease, schizophrenia and autism. In the former illness, reduced blink rate signifies a worsening of the illness and a significant increase in blink rate in patients treated with dopamine agonist may be a harbinger of agonist-induced dyskinesia. In schizophrenia, increased blink rate, even in medication-naive subjects, may signify involvement of the structures that regulate blinking. This is important because these structures are rarely invoked as sites of potential pathophysiological import in schizophrenia. Similar considerations apply to autism except that increased blinking more clearly differentiates this disorder from other forms of retardation.