Six depressed mentally retarded adults were treated with fluoxetine in an open trial. Five patients significantly improved, and one patient partially improved, after treatment with fluoxetine. Their mean Hamilton Depression Rating Scale score was significantly reduced after treatment. These results suggest that fluoxetine is a safe and effective treatment for depression in mental retardation. Some potential advantages of using fluoxetine in this clinical population are discussed. Additional controlled research studies are needed to confirm these findings.