Pristanic acid (Prist) accumulates in some peroxisomal disorders characterized by neurologic dysfunction and brain abnormalities. The present work investigated the in vitro effects of Prist on important parameters of energy metabolism in brain cortex of young rats. CO(2) production from labeled acetate and the activities of the respiratory chain complexes I-IV, creatine kinase and synaptic Na(+), K(+)-ATPase were measured. Prist decreased CO(2) production and the activities of complexes I, II and II-III. Prist also reduced Na(+), K(+)-ATPase activity, but did not affect the activity of creatine kinase. Considering the importance of the citric acid cycle and the electron flow through the respiratory chain for brain energy production and of Na(+), K(+)-ATPase for the maintenance of membrane potential, the present data indicate that Prist compromises brain bioenergetics and neurotransmission. It is presumed that these pathomechanisms may be involved in the neurological damage found in patients affected by disorders in which Prist accumulates.