Although some previous studies assert that an association between schizotypy and loss of hand dominance is well established, the prevailing use of student populations, small effect sizes and arbitrariness of handedness classification suggest that this tentative association merits further investigation. The association of schizotypy and loss of hand dominance was examined using four samples. The first comprised 353 randomly selected individuals from the general community, the second comprised 131 screened volunteers participating as control subjects in a family study of schizophrenia, the third included 97 full siblings of schizophrenia patients, and the fourth consisted of 176 schizophrenia patients from the same study. The samples of screened volunteers and nonpsychotic siblings were used to replicate results from the community sample and to test the hypothesis that an increase in genetic liability is related to the association of schizotypal traits and mixed handedness. The results demonstrated that mixed handedness and schizotypy traits were unrelated in the representative sample from the community. This finding was replicated in the sample of screened volunteers, while siblings of schizophrenia patients showed a trend in the direction of the hypothesised relationship. In contrast, there was an expected significant but low in magnitude association between loss of hand dominance and the Schizotypal Personality Questionnaire factor of Cognitive Perceptual Dysfunction in schizophrenia patients. (c) 2005 Elsevier Ireland Ltd. All rights reserved.