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ABSTRACT. The use of fluoxeiine to treat chronic depression and associated self‐injurious behaviour (SIB) in a woman with severe mental retardation and a man with profound mental retardation is reported. In the first case, behavioural monitoring of treatment response revealed a dramatic decrease in SIB and a normalization of the woman's sleep disturbance. In the second case, SIB and the use of mechanical restraint decreased substantially. In both cases, anecdotal reports also indicated a diminution of other depressive symptoms. These cases highlight the need to consider an affective disorder as a cause of SIB in persons with severe and profound developmental disabilities. The behaviour monitoring system proved to be a practical aid in the diagnosis of depression and evaluation of antidepressant treatment in individuals who were incapable of self‐report.