We have examined the expression of cyclin dependent kinase (cdk) 5 protein kinase and p35nck5a, its activator subunit, during postnatal neurogenesis in rat cerebellum, using mono-specific antibodies. Both cdk5 and p35nck5a are present and associated in proliferative stages, although cdk5-p35 kinase activity is barely detectable. Cdk5-p35 activity, but not the expression of either subunit, increases up to 6-fold during neuronal differentiation. Since we observe that cdk5 is phosphorylated on tyrosine in proliferative, but not in post-mitotic stages, we suggest that post-translational regulatory mechanisms control cdk5-p35 protein kinase activity during neurogenesis.