Creatine kinase (CK) activity was found decreased in the brains of patients with Alzheimer's disease (AD) and Pick's disease (PD). However, the decrease of total CK activity in AD was more pronounced than in PD. Analysis of the activity of two CK isoforms, BCK and ubiquitous mitochondrial CK, demonstrated that the decrease of total CK activity in AD and PD was related to the decrease of BCK activity. The decline of CK activity both in AD and PD correlated well with the decline of the content of immunoreactive BCK in brain extracts. The BCK mRNA level in AD and PD was not significantly different from control patients and could not be the primary reason for decreases in CK content and activity. The decreased level of BCK in AD and PD brains might be caused by posttranscriptional events, which could affect the translation of BCK mRNA and/or lead to the inactivation and degradation of the enzyme. Because CK is sensitive to oxidative modification, it is possible that the changes observed in this study result from free radical damage.