The son of the Rev John Pye Smith, DD, FRS, a well-known Sheffield Nonconformist minister and geologist; the son inherited his father's industry, love of knowledge, and religious principles. Pye Smith went to Mill Hill School and was then articled to Ashwell, a City practitioner; he next studied at Guy's Hospital. There he learnt from Astley Cooper, Bright, and Addison, dressed for Aston Key, and attended the practice of Travers and Green at St Thomas's Hospital. He became acquainted with Hilton, Hodgkin, and John Blackburn. He then attended the hospitals in Paris, studied under Magendie, and made friends of Gustave Monod and of Bovet, at Neufchatel. He thus became a good anatomist and pathological draughtsman. He next entered a partnership in the City, married, moved to Billiter Square, and practised by himself. Between 1840 and 1850 he was most successful as a coach preparing for the London University degree, counting four pupils - Pavy, Habershon, J J Phillips, and his own son, Philip Henry Pye Smith - who all became Physicians to Guy's Hospital. He was Secretary to the Hunterian Society and was one of the original members of the Pathological Society. He moved to 275 Mare Street, Hackney, and practised there for twenty years. Tall, with fine features and slender figure, courteous in manner, he had the gift of acquiring friends and of sympathizing with patients. He would give much time to individual cases, and anxiety as to results often disturbed his peace. He retired to Sevenoaks in 1874, died there on March 9th, 1885, and was buried in Abney Park Cemetery. He was survived by his widow and eight children. The third son was Rutherford John Pye Smith (qv).