Dropout from prophylactic neuroleptic treatment is one major reason for relapse in schizophrenia patients. There is a lack of prospective studies on factors that predict medication adherence. We investigated factors suspected to predict dropout from continuous neuroleptic treatment in a 2-year prospective study involving 122 outpatients with a DSM-III-R diagnosis of schizophrenia. Forty-two (34.4%) were classified as patient-related dropouts. No significant difference between compliant patients and dropouts was found with regard to sociodemographic variables, except that compliant patients were significantly older. Also, no differences in psychopathology were seen at the beginning of treatment, but compliant patients had a longer duration of illness. Compliant patients had higher doses of neuroleptics in the initial stabilization phase and correspondingly showed more extrapyramidal signs. Physicians rated compliant patients from the beginning as more cooperative. These patients also showed significantly higher scores in positive treatment expectations. In a stepwise regression analysis, positive illness concepts, the global assessment of functioning (GAF), and the physicians' view of patients' cooperation predicted 19 percent of the variance. We concluded that the prediction of dropouts is insufficient and remains largely an unsolved problem. Future research should focus more on context factors in the search for clinically meaningful explanations of patient dropout from treatment.