Neuroplastin is a cell adhesion molecule of the immunoglobulin superfamily that exists in two splice isoforms, np65/np55, and that was reported to play a prominent role in synaptic plasticity processes. The splice isoform np65 associates with synapses in an activity-dependent manner and has been shown to play a role for the induction of hippocampal long-term potentiation in rodents. We have therefore analyzed the distribution of neuroplastins in human brain. Neuroplastin is present in many neuronal cell types of the forebrain and cerebellum and immunoreactive label covers the cell soma, neurites and also puncta in the neuropil were visible. Interestingly, we found some remarkable species differences in the expression patterns of neuroplastins between the human and the rodent brain. In human brain np65 is prominently present in cerebellum while np55 is the predominant isoform in mouse and rat cerebellum. Moreover, the parasagittal stripe-type of staining seen with np55 in mouse cerebellum is not found in human brain. In addition we found no segregation of np65 immunolabel in hippocampal subregions like it was reported previously for the rat. These results might indicate different cellular functions of the molecule in different species.