Previous studies have demonstrated that cerebrospinal fluid (CSF) from the lateral ventricle of patients without disturbance of sensorium or intracranial pressure, contains 15 to 30 nM 3',5' cyclic adenosine monophosphate (cAMP). The concentration of this cyclic nucleotide was measured by radioimmunoassay in 133 samples of CSF from the lateral ventricle of 26 patients who were comatose following acute head trauma for periods up to 40 days. Concentration of CSF cAMP in diminishing coma Grades V, IV, III, II, and I was 1.5 +/- 0.1 nM; 1.24 +/- 0.34 nM; 3.14 +/- 0.7 NM; 10.06 +/- 3.47 nM; and 13.36 +/- 1.38 nM, respectively. After the sensorium cleared (coma Grade 0), cAMP was 22.0 +/- 1.7 nM. The correlation between the grade of coma and cAMP concentration was -0.80 (p greater than 0.01). These results imply that alteration in the level of consciousness following head trauma is associated with a disturbance of cAMP metabolism within the central nervous system. Possible mechanisms explaining this observation as well as therapeutic implications are discussed.