Previous studies of the auditory P300 event-related potential (ERP) from our laboratory have reported a left- greater than right-sided attenuation in medicated chronic schizophrenics compared with normal controls. A possible confound in these studies has been the use of the linked-ear reference (LER), which has been criticized on the grounds that it might either induce or suppress topographic asymmetries. To test the effects of LER on P300 asymmetries in schizophrenia, we recorded ERPs with both LER and a nose reference (NR) in a group of 20 chronic medicated schizophrenics and in group of 20 age-matched normal controls. We here report: (1) confirmation of our previous P300 findings of left temporal scalp region deficit using both LER and NR with a 28-electrode montage; this feature was prominent in the wave form associated with the target stimulus, without the use of the wave form subtractions of our previous studies; (2) no statistically significant topographic differences between the LER and NR for either the schizophrenic or normal subjects; and (3) better performance of the LER in differentiating schizophrenics versus normal controls, due to lower wave form variability. We conclude that the LER is preferable for studies using subject groups and methodology similar to the present study.