The presence of cimetidine in the incubation medium of rat brain mitochondria caused decreased oxygen uptake, especially during oxidative phosphorylation (state 3). This inhibition of the respiratory control and of ATP synthesis was dose-dependent. The same observations were made for hepatic mitochondria. The significance of these results is discussed in terms of both the neurological side-effects of cimetidine and its effect on regulatory mechanisms of cerebral or hepatic blood flow.