The skin-conductance orienting response (SCOR) in schizophrenia is often characterized by either nonresponding or delayed habituation to repeated nonsignal tones. These abnormalities are poorly related to other dimensions of schizophrenia. In the present study, we confirmed that about 50% of patients with chronic schizophrenia are SCOR nonresponders. Nonresponders, however, did not differ from responders on postmorbid psychiatric or pharmacological course, and we therefore could not confirm the hypothesis that course of illness follows a more marked pattern of increasing severity in nonresponders. Performance on the Wisconsin Card Sorting Test (WCST) was particularly poor in a subgroup of responders who exhibited either delayed habituation and/or dishabituation of SCORs to tones applied after a short rest period. It is possible that pathology of the prefrontal cortex mediates the SCOR abnormalities that characterize schizophrenic patients who perform poorly on the WCST.