Plasmas, cerebrospinal fluid and urine were sampled from 22 patients with cerebral hemispheric infarction and analyzed for cyclic AMP. The following observations were made: (1) In mild cases with slight dysarthria and/or hemiparesis but without disturbance of consciousness (Group I), cyclic AMP in peripheral venous plasma (PVP) remained over the normal lowest level more than 10 days after the onset. Patients with apparent neurological deficits could be divided into two groups. In one group, cyclic AMP in PVP decreased to a subnormal level within about 5 days after the onset of stroke (Group II). In another group (Group III), such a decrease was not observed. Brain isotope scintigrams were revealed negative in Group I. The size of brain infarct as judged by isotope uptake was larger in Group III than in Group II, except for a few cases in which the lesion was restricted in the basal ganglionic region. (2) No clinical significance was, however, found in the time course of cyclic AMP levels in internal jugular venous or femoral arterial plasma, or in cerebrospinal fluid, or of the daily amount of cyclic AMP excretion into urine. (3) Cerebral arterio-venous difference of cyclic AMP was negative in most of the cases.