Attention deficits are common in schizophrenics and sometimes reported in their healthy relatives. The aim of this study was to analyse the behavioural performance and the brain activation of healthy siblings of schizophrenic patients during a sustained-attention task. Eleven healthy siblings of schizophrenic patients and eleven matched controls performed a Continuous Performance Test (CPT), during 1.5 T fMRI. The stimuli were presented at three difficulty-levels, using different degrees of degradation (0, 25 and 40%). There were no significant differences in CPT performance (mean reaction time and percentage of errors) between the two groups. Performance worsened with increasing degradation in both groups. Differences were found when comparing the BOLD signal change in the medial frontal gyrus/dorsal anterior cingulate, right precentral gyrus, bilateral posterior cingulate and bilateral insula. The most evident between group differences were observed in the left insula/inferior frontal gyrus: siblings showed a larger activation during wrong responses and a reduced activation during correct responses in the degraded runs. In conclusion, healthy siblings of schizophrenic patients showed differences in brain function in several brain regions previously reported in schizophrenic subjects, in the absence of behavioral attention deficits. The differences were greater in the two more difficult levels of attention demand and might be expressions of altered and/or compensatory mechanisms in subjects at increased risk for schizophrenia.