6-Hydroxydopamine (6-OHDA) injected into the lateral cerebral ventricles of rats impaired their exercise performance until exhaustion (treadmill run and swimming). The injected rats displayed significantly less training-induced improvement of swimming performance than did the control animals. Reduced performance also was seen in adult rats treated intraperitoneally with 6-OHDA in the neonatal or adult periods. The functional impairment can be explained by the neurotoxic action of 6-OHDA on monoamine brain structures (substantia nigra and locus ceruleus) and/or on peripheral sympathetic innervation, the latter assessed by histofluorescence of the iris muscle. The possible contribution of lacticacidemia to the reduced tolerance to stress of 6-OHDA-treated rats by the intracerebroventricular route also is considered.