BACKGROUND: Previous preliminary reports have suggested potential interactions between microcytic anaemia and mood disorders. In particular, heterozygous beta-thalassaemia has been implicated in the bipolar spectrum. This study surveyed relevant haematological parameters in a large sample of psychiatric outpatients with the aim of clarifying previous observations. METHODS: Mean Corpuscular Volume (MCV) was analysed in 1014 consecutive patients diagnosed according to modified Research Diagnostic Criteria (RDC). Haemoglobin electrophoresis and/or chromatography was performed in blood samples from 143 patients with reduced MCV. Prevalence of heterozygous beta-thalassaemia was estimated based on the rates of patients with reduced MCV and increased haemoglobin A2 concentration. RESULTS: MCV lower than 80 mu3 was found in greater proportions among bipolar compared with the remaining RDC subgroups (183/732 = 25.0% versus 51/282 = 18.1%; p = 0.02; relative risk = 1.38; Fisher's exact test). This difference can mainly be attributed to heterozygous beta-thalassaemia, the estimated prevalence of which was 16.4% among bipolar and 9.9% among non-bipolar subgroups (p = 0.01; relative risk = 1.65). CONCLUSION: The results are consistent with the hypothesis that heterozygous beta-thalassaemia might play a role as a susceptibility factor in bipolar spectrum disorders in specific populations.