The mutant mice tottering, leaner and the compound heterozygous tottering/leaner exhibit varying degrees of several abnormal neurological phenotypes including petit mal-like epilepsy, ataxia and an intermittent myoclonus-like movement disorder. Aberrant expression of tyrosine hydroxylase in cerebellar Purkinje cells of tottering, leaner and tottering /leaner mice has been observed previously [Austin M. C. et al. (1992)Molec. Brain Res.15, 227–240; Hess E. J. and Wilson M. C. (1991)Neuron6, 123–132]. In the present study, the distribution of tyrosine hydroxylase expression was compared with that of Zebrin II in Purkinje cells of adult homozygous tottering and compound heterozygous tottering/leaner mutant mice using single and double immunocytochemistry and double immunofluorescence. The pattern of Zebrin II expression in the cerebella of the mutant mice was identical to that described for normal mice [Hawkes R. et al. (1985)Brain Res.333, 359–365; Hawkes R. and Leclerc N. (1987)J. comp. Neurol.256, 294¯1]. In addition, sections through tottering and tottering/leaner cerebella demonstrated an exact correspondence between the bands of tyrosine hydroxylase immunoreactivity and bands of Zebrin II immunoreactivity. Similarly, the compartments of the Purkinje cell layer which were negative for Zebrin II staining were also negative for tyrosine hydroxylase immunoreactivity. This study provides evidence that the cerebellar Purkinje cells of tottering and tottering/leaner mice were able to express a normal gene product, Zebrin II, in a normal spatial pattern and the same Purkinje cells can also express an aberrant gene product, tyrosine hydroxylase. This abnormal gene expression may indicate that at least some Purkinje cells in these mutant mice are not functioning normally. This possibility, taken together with the morphological changes observed in many mutant Purkinje cell axons, suggests that Purkinje cell function could be altered in tottering and tottering/leaner mice, thereby contributing to the neurological abnormalities exhibited by these mice. It is also possible that alteration in function of mutant Purkinje cells could correlate with the rostrocaudal zonation pattern described in this study.