From the time of the Spanish influenza pandemic in 1918 to the present seclusion of volunteers in quarantine units, either modified hotels, Phase I units or specially constructed clinics, have been key in investigating new vaccines and antivirals. Carefully selected healthy, young volunteers undergo a 10-12-day sojourn under intense medical supervision. Clinical sampling includes nasal and throat washes for virus recovery, blood for clinical chemistry, analysis of B- and T-cell response and, more recently, analysis of human genes responding to infection. The authors' studies are resulting in new developments of universal influenza vaccines that could stimulate and prime CD4 and CD8 cells to shared epitopes in all influenza A viruses. Ethnographic study has noted an absence of quarantine stress in the volunteers for the first time.