Whereas etiological heterogeneity of the various types of schizophrenia has been repeatedly proposed, relatively few attempts have been made to separate the component diseases. Using a strategy focusing on bimodal distributions within several relevant domains of schizophrenia, we demonstrate that currently available data on schizophrenia patients are consistent with the hypothesis that some of these patients have an ongoing neurodegenerative disease, whereas others do not. We review studies (longitudinal and cross-sectional) documenting progressive increases in ventricular size, accelerated loss of brain tissues, progressive delays in treatment response, and neurochemical (magnetic resonance spectroscopy) and neurophysiological (P300) indices, all of which are consistent with ongoing cerebral degeneration in a significant subgroup of schizophrenia patients. These lines of evidence converge on a conceptualization of schizophrenia as being composed of several etiologically distinct processes, with one subset of psychotic patients evidencing progressive brain degeneration. We conclude with a discussion of possible etiologies for this condition.