Thirty-nine patients with chronic schizophrenia for whom hospitalization was clinically indicated received haloperidol for 4 to 6 weeks in a standardized dose schedule. Responders were compared with nonresponders for family history, baseline symptom factors, and ventricle-brain ratio (VBR). The lifetime risk for schizophrenia spectrum disorders was higher among first-degree relatives of nonresponders than among first-degree relatives of responders. Treatment responders had higher baseline scores on the factors of activation and hostile-suspiciousness, but the groups did not differ in any other baseline symptom factor or in VBR. The authors suggest that there is an association between failure to respond to drugs and genetic loading for schizophrenia spectrum disorders.