Sam Greenhouse began his involvement in mental disorders research in 1954 when appointed chief of the Theoretical Statistics and Mathematics section at the National Institute of Mental Health. He remained with the NIMH until 1966. Despite moving on to several other positions at the NIH and at the university during the ensuing years, he continued as a consultant to NIMH investigators. He also participated activity as an advisor and co-investigator on a number of important collaborative research programmes launched by the Institute in the 1970s and 1980s. His contributions to the design and methodology of the first clinical trials of drugs for the treatment of schizophrenia, to research aimed at revising the national and international classification systems for the mental disorders, and his participation in the planning of the first attempt to use the collaborative research model to test hypotheses about the genesis of a specific mental disorder (depression), are described. Finally, the signal importance of the 'profile analysis of variance' method that he and Seymour Geisser developed, to research on personality and mental disorders, is examined in detail. The authors describe applications of the method in their own research on the classification of the mental disorders, predicting response to drug treatment and the variations in the expression of mental illness across different cultures. Sam worked in mental health during an era of revolutionary changes in the diagnosis and treatment of mental disorders. The field was acutely aware of his many contributions to the progress of research and his colleagues are very grateful to have had the opportunity to work with him. Copyright (C) 2003 John Wiley Sons, Ltd.