He was one of the inventors and developers of the life-saving method called oral rehydration therapy for adults and children suffering fluid loss from cholera and other infectious diarrheal illnesses.

After a post-doctoral fellowship from the National Institute of Arthritis and Metabolic Disease in electrophysiology at Harvard-affiliated Beth Israel Hospital in Boston (1968–1970), he was appointed Assistant Professor of Clinical Medicine, Johns Hopkins University School of Medicine at Baltimore City Hospital, and Lecturer, Department of International Health, Johns Hopkins University School of Hygiene and Public Health (1970–1973).

In that time, he introduced oral rehydration therapy on the White River Apache Indian Reservation with a grant from the National Institute of Allergy and Infectious Diseases.

It was demonstrated that children would voluntarily drink as much of the solution as needed to restore hydration; and that rehydration and early re-feeding would protect their nutrition.

From 1990 to 1993, with a United Nations Food and Agriculture Organization team, Hirschhorn conducted research on pesticide poisoning in Indonesian farmers.

In those intervening years, he also served as a consultant to the World Health Organization Tobacco-Free Initiative, conducting research on tobacco industry documents.