Brain type creatine kinase (BB) isoenzyme was measured using a highly sensitive and specific radioimmunoassay procedure (limit of detection, 1 microgram/l of sample) in two schizophrenic populations, an acute non-medicated group consisting of 35 subjects and a chronic group of 15 subjects. Since the assay can also measure the B subunit of MB isoenzyme, patients were selected so as to exclude subjects with possible heart, kidney or other ailments which might result in an increased serum creatine kinase B subunit. Both the acute schizophrenics (3.0 +/- 0.23) mean S.E.M. and the chronic schizophrenics (2.9 +/- 0.33) had serum levels of creating kinase BB similar to those of controls (2.8 +/- 0.21) and non-cardiac patients (3.5 +/- 0.58). Patients having myocardial infarction or neurovascular surgery had elevated creatine kinase B subunit. Similar but much less sensitive quantitative results were obtained using agarose multizonal electrophoresis. Despite a recent report that human brain contains the creatine kinase MM isoenzyme, analysis of five human brains using DEAE-Sephadex-A50 for MM isoenzyme fractionation, followed by immunodiffusion analysis of concentrated eluate revealed no detectable MM isoenzyme. The results from these studies suggest that the elevated serum creatine kinase activity of schizophrenic patients is most likely not of brain origin.