One of the primary approaches in experimental brain research is to investigate the effects of specific destruction of its parts. Here, several neurotoxins are available which can be used to eliminate neurons of a certain neurochemical type or family. With respect to the study of dopamine neurons in the brain, especially within the basal ganglia, the neurotoxin 6-hydroxydopamine (6-OHDA) provides an important tool. The most common version of lesion induced with this toxin is the unilateral lesion placed in the area of mesencephalic dopamine somata or their ascending fibers, which leads to a lateralized loss of striatal dopamine. This approach has contributed to neuroscientific knowledge at the basic and clinical levels, since it has been used to clarify the neuroanatomy, neurochemistry, and electrophysiology of mesencephalic dopamine neurons and their relationships with the basal ganglia. Furthermore, unilateral 6-OHDA lesions have been used to investigate the role of these dopamine neurons with respect to behavior, and to examine the brain's capacity to recover from or compensate for specific neurochemical depletions. Finally, in clinically-oriented research, the lesion has been used to model aspects of Parkinson's disease, a human neurodegenerative disease which is neuronally characterized by a severe loss of the meso-striatal dopamine neurons. In the present review, which is the first of two, the lesion's effects on physiological parameters are being dealt with, including histological manifestations, effects on dopaminergic measures, other neurotransmitters (e.g. GABA, acetylcholine, glutamate), neuromodulators (e.g. neuropeptides, neurotrophins), electrophysiological activity, and measures of energy consumption. The findings are being discussed especially in relation to time after lesion and in relation to lesion severeness, that is, the differential role of total versus partial depletions of dopamine and the possible mechanisms of compensation. Finally, the advantages and possible drawbacks of such a lateralized lesion model are discussed.