In-vivo heat-shock induced heat shock factor (HSF) DNA-binding activity and accumulation of heat shock protein (hsp)70 mRNA in newborn and adult rat cerebellum was studied. We identified a high basal level of c-Jun N-terminal kinase (JNK) and p38 MAP kinase phosphorylation in the cerebellum, independently of age. Hyperthermia increased JNK1, decreased JNK2 but did not modify JNK3 phosphorylation in the newborn cerebellum, whereas decreased the phosphorylation of both JNK1 and JNK3 in adult rats. During recovery from hyperthermia, JNK2 phosphorylation returned to control level in the newborn, JNK1 appeared hyperphosphorylated only in the newborn, and JNK3 in all animals. JNK2 never appeared phosphorylated in the adult cerebellum. Hyperthermia increased p38 MAP kinase phosphorylation in the cerebellum, with different trends in newborn and adult rats during recovery. Heat shock increased extracellular signal-regulated kinase phosphorylation concomitant to tyrosine kinase receptor activation (epidermal growth factor-receptor in the newborn and insulin-like growth factor-receptor in the adult cerebellum). The behavior of stress kinases may underlie a different age-related vulnerability to heat stress of the cerebellum.