Casein kinase 2 is present in the brain, including the hippocampus. It is associated with long-term potentiation and is known to be involved in phosphorylation of proteins potentially important for neuroplasticity, but regulation of its activity in neuronal cells is not yet known. In the present work, it was found that brain-derived neurotrophic factor and neurotrophin-4 control the activity of casein kinase 2 in hippocampal slices of adult rat. It is shown that: (i) treatment of slices for 4 h with the neurotrophins results in a five-fold increase in the activity of cytosolic casein kinase 2; (ii) this effect does not require protein synthesis. In addition, using calcium chelators, phospholipase inhibitors and protein kinase inhibitors, evidence is provided that: (i) neurotrophin-induced activation of casein kinase 2 is dependent on the availability of intracellular calcium due to stimulation of phospholipase C; (ii) both a tyrosine kinase(s) and a serine/threonine kinase(s) convey the signal of calcium. Since there is now accumulating evidence for involvement of brain-derived neurotrophic factor, intracellular calcium, tyrosine kinases and serine/threonine kinases in the regulation of synaptic plasticity, it is suggested that the signalling cascade detected here might contribute to control of synaptic strength in the hippocampus.