The original sandstone complex, known initially as Tarban Creek Lunatic Asylum, was designed by the Colonial Architect, Mortimer Lewis, between 1836 and 1838.

[2] The first supervisor was John Thomas Digby, who sought to improve the treatment of the mentally ill, as did his successor, Frederick Norton Manning.

Before accepting, Manning went overseas and studied methods of patient care and administration of asylums; on his return to Sydney, he submitted a notable report.

He was appointed to Tarban Creek on 15 October 1868 and immediately reported on the isolation of patients from their relations in accommodation best described as 'prison-like and gloomy', the inadequate facilities for their gainful employment and recreation and the monotonous diets deficient in both quantity and quality.

In January 1869, the asylum's name was changed to the Hospital for the Insane, Gladesville, wherein patients were to receive treatment rather than be confined in a 'cemetery for diseased intellects'.