We investigated whether prepulse inhibition of the startle response is reduced in siblings of schizophrenia patients compared to age- and sex-matched healthy controls. Nineteen unaffected biological siblings and 19 controls were assessed on prepulse inhibition by monaural and binaural acoustic prepulse stimuli, with the startle stimuli always presented binaurally. There was significantly less prepulse inhibition in siblings, compared to controls, with binaural prepulse stimuli, as also seen previously in schizophrenia patients. The difference between siblings and controls in prepulse inhibition with the left or right ear prepulse stimuli was not significant because of a pronounced increase in prepulse inhibition with monaural, relative to binaural, prepulses in the sibling group. High schizotypal ratings were mildly associated with reduced prepulse inhibition. Prepulse inhibition may provide a useful measure in the search for schizophrenia genes.