We investigated the cellular distribution of three calcium sensor proteins, visinin-like protein-1 (VILIP-1), VILIP-3, and hippocalcin, in different rat brain areas after repeated administration of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine. In comparison to controls we observed an increase in the density of VILIP-1 immunoreactive (IR) hippocampal interneurons and presubicular nerve cells in ketamine treated rats, whereas the density of VILIP-1 expressing cells was decreased in the Nuc. accumbens of these rats. No alterations were seen in the distribution patterns of VILIP-3. The density of hippocalcin-expressing neurons was increased in the cingulate cortex of drug-treated rats. Our experiments show that repeated injections of subanesthetic doses of ketamine induce subtle changes in the cellular distribution of calcium sensor proteins which in part resemble those recently described in postmortem brains of human schizophrenics [Bernstein, H.-G., Braunewell, K.-H., Spilker, C., Danos, P., Baumann, B., Funke, S., Diekmann, S., Gundelfinger, E.D. and Bogerts, B., NeuroReport, 13 (2002) 393-396].