Levels of the histamine metabolites, tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA), and metabolites of other aminergic transmitters and of norepinephrine were measured in cerebrospinal fluid of 36 inpatients with chronic schizophrenia and eight controls. The mean t-MH level from controls was nearly identical to the levels seen previously in healthy volunteers. Compared with controls, the mean level of t-MH in the schizophrenic patients was 12.6-fold (higher (p=0.006); 21 of the patients had levels exceeding the range of controls. There was no significant difference (p>0.05) in levels of other analytes, although the levels of t-MH correlated significantly with those of t-MIAA, homovanillic acid, 3,4-dihydroxyphenylacetic acid, norepinephrine, 3-methoxy-4-hydroxyphenylglycol and 5-hydroxyindoleacetic acid. The difference in levels of t-MH were not attributable to medication, since those taking (n=10) or withdrawn from (n=26) neuroleptic drugs had nearly the same mean levels of t-MH; each group had higher levels than controls (ANOVA: p<0.05). Patients with or without tardive dyskinesia showed no significant differences in means of any analyte. Only levels of t-MH-among those with schizophrenia correlated with positive symptom scores on the Psychiatric Symptom Assessment Scale (r(s)=0.45, p<0.02). The elevated levels of t-MH in cerebrospinal fluid, which represent histamine that was released and metabolized, suggest increased central histaminergic activity in patients with chronic schizophrenia.