Systemic blood cyclic AMP levels were elevated but urinary excretion was unaltered in patients with recent cerebral infarction. Cerebral venous levels for cyclic AMP were significantly higher than arterial levels. CSF cyclic AMP levels were also elevated. After intravenous 10% glycerol, CSF cyclic AMP levels decreased and cerebral A-V differences were reduced. Elevation of cyclic AMP levels in plasma may be due to alteration of neuroendocrinal function after cerebral infarction and contributed to in part by release from infarcted brain. Cyclic AMP release into cerebral venous blood and CSF suggests (1) blood brain barrier damage and (2) extracellular cyclic AMP accumulation in infarcted brain secondary to abnormal neurotransmitter release and/or impaired cellular function which appears to be partially reversed by glycerol.