It is well known that Parkinson's disease occurs more commonly in older people and men are more frequently affected than women. Animal studies in models of the disease mainly use young male animals. The effects of aging on the neurochemical changes in the dopaminergic system have been extensively studied, however, data on comparative behavioral consequences of lesions of the dopaminergic system in aging and in female animals are limited. The aim of the present study was to give a detailed comparative behavioral analysis of young and aging male and female rats following 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. Young males and females, as well as aging males and females underwent 6-OHDA-induced lesion of the substantia nigra. Behavioral analysis in an open-field was performed before the injury, and 1 and 10 days after the operation. Tyrosine-hydroxylase (TH) immunohistochemistry was done in order to assess the dopaminergic cell loss in the substantia nigra. It was found that both young and aging male animals were more susceptible to 6-OHDA than females: female rats had a significantly less dopaminergic cell loss and responded to 6-OHDA with a significantly higher degree of behavioral recovery after the injury. Although the dopaminergic cell loss was not significantly different between young and aging animals of the same sex, aging rats showed more severe behavioral deficits. In summary, our present results showed clear age- and gender differences in the behavioral and histological outcome following 6-OHDA lesion of the substantia nigra.