Arriving in Paris (1778), he supported himself for a number of years by translating scientific and medical works and by teaching mathematics. During that period he also began visiting privately confined mental patients and writing articles on his observations. In 1792 he became the chief physician at the Paris asylum for men, Bicêtre, and made his first bold reform by unchaining patients, many of whom had been restrained for 30 to 40 years. He did the same for the female inmates of Salpêtrière when he became the director there in 1794.

Discarding the long-popular equation of mental illness with demoniacal possession, Pinel regarded mental illness as the result of excessive exposure to social and psychological stresses and, in some measure, of heredity and physiological damage. In Nosographie philosophique (1798; “Philosophical Classification of Diseases”) he distinguished various psychoses and described, among other phenomena, hallucination, withdrawal, and a variety of other symptoms.

Pinel did away with such treatments as bleeding, purging, and blistering and favoured a therapy that included close and friendly contact with the patient, discussion of personal difficulties, and a program of purposeful activities. His Traité médico-philosophique sur l'aliénation mentale ou la manie (1801; “Medico-Philosophical Treatise on Mental Alienation or Mania”) discusses his psychologically oriented approach.