A tentative model for conceptualizing the interplay of vulnerability factors, stressors, and protective factors in the course of schizophrenia is discussed. A study of the initial years after a first schizophrenic episode is testing the predictive role of key factors. During an initial 1-year period of depot antipsychotic medication, independent life events and expressed emotion were found to predict the likelihood of psychotic relapse. Initial analyses indicate that independent life events play less of a role in relapse prediction during a medication-free period. These results suggest that maintenance antipsychotic medication raises the threshold for return of psychotic symptoms, such that relapses are less likely unless major environmental stressors occur. A low expressed emotion environment may be a protective factor.