Ca2+-calmodulin-dependent protein kinase II (CaMKII) and protein phosphatase 2B (calcineurin) play critical roles in the formation of nerve cell responses to incoming Ca2+ signals. The studies report here addressed how single seizures might affect the functioning of these enzymes. Sounds (80 dB, 12–15 kHz) induced single convulsions in male Krushinskii–Molodkina rats, which have an inherited predisposition to audiogenic seizures. Biochemical investigations were performed two days after seizures. Immunoblotting studies with specific monoclonal antibodies demonstrated increases in the level of the neurospecific α subunit of CaMKII in the sensorimotor cortex and hippocampus of the rats of the experimental group, as compared with controls. The hippocampus of rats which had had seizures also showed increases in the catalytic subunit of calcineurin. CaMKII activity in the hippocampus and cortex of postseizure rats increased, though that of the Ca2+-calmodulin-independent functional form of the enzyme did not change. It is suggested that the long-term changes seen here may represent an adaptive mechanism induced by convulsive activity and directed to increasing the threshold of neuron excitability in the brain.