Constructed at a cost of $1.5 million, with the estimated yearly per capita cost of patients being $3,000 the hospital originally consisted of two main center buildings, housing the administration, with four radiating wings. The administration building measured 90 by 60 feet (18 m), with a 130 feet (40 m) high tower. The kitchens, laundries,chapel, and dormitories for the attendants were in a connecting 180 by 60 feet (18 m) building in the rear. In the rear was the boiler house of 70 feet (21 m) square, with boilers 450 horsepower (340 kW), used for heating and ventilation. Middleton Pond supplied the hospital its water. On each side of the main building were the wings, for male and female patients respectively, connected by small square towers, with the exception of the last ones on each side, which are joined by octagonal towers. The former measured 10 feet (3.0 m) square, and were used to separate the buildings. The outermost wards were reserved for extreme patients. West side was male, east was female.
Over the years, newer buildings were constructed around the original Kirkbride, as well as alterations to the Kirkbride itself, such as a new gymnasium/auditorium on the area of the old kitchens and multiple solaria added onto the front of the wards.
Most of the buildings on campus were connected by a confusing labyrinth of underground tunnels, also constructed over the years. Many of the Commonwealth institutions for the developmentally delayed and the mentally ill at the time were designed with tunnel systems, to be self-sufficient in wintertime. There was a tunnel that ran from a steam/power generating plant (which still exists to provide service to the Hogan Regional Center) located at the bottom of the hill running up to the hospital, along with tunnels that connected the male and female nurses homes, the "Gray Gables", Bonner Medical Building, machine shops, pump house, and a few others. The system of tunnels branched off like spokes from a central hub behind the Kirbride building (in the vicinity of the old gymnasium) leading to different wards of the hospital and emerging up into the basements. This hub was also an underground maintenance area of sorts. Some nicknamed it "The Wagon Wheel" due to its design. These older brick and cobblestone tunnels were used in the production of the movie Session 9. The original plan was designed to house 500 patients, with 100 more possible to accommodate in the attic. However, by the late 1930s and 1940s, over 2,000 patients were being housed, and overcrowding was severe. People were even held in the basements of the Kirkbride.
While the asylum was originally established to provide residential treatment and care to the mentally ill, its functions expanded to include a training program for nurses in 1889 and a pathological research laboratory in 1895. In the 1890s, Dr. Charles Page, the superintendent, declared mechanical restraint unnecessary and harmful in cases of mental illness. By the 1920s the hospital was operating school clinics to help determine mental deficiency in children. Reports were made that various, and inhumane shock therapies, lobotomies, drugs, and straitjackets were being used to keep the crowded hospital under control. This sparked controversy. During the 1960s as a result of increased emphasis on alternative methods of treatment, deinstitutionalization, and community-based mental health care, the inpatient population started to decrease. On June 24, 1992, the hospital closed. After abandonment, the wards and buildings were left to decay and rot for many years until the demolition.