We previously demonstrated that olfactory cultures from individuals with schizophrenia had increased cell proliferation compared to cultures from healthy controls. The aims of this study were to (a) replicate this observation in a new group of individuals with schizophrenia, (b) examine the specificity of these findings by including individuals with bipolar I disorder and (c) explore gene expression differences that may underlie cell cycle differences in these diseases. Compared to controls (n = 10), there was significantly more mitosis in schizophrenia patient cultures (n = 8) and significantly more cell death in the bipolar I disorder patient cultures (n = 8). Microarray data showed alterations to the cell cycle and phosphatidylinositol signalling pathways in schizophrenia and bipolar I disorder, respectively. Whilst caution is required in the interpretation of the array results, the study provides evidence indicating that cell proliferation and cell death in olfactory neuroepithelial cultures is differentially altered in schizophrenia and bipolar disorder.