Unknown tissue reservoirs of HIV may contribute to viral re-emergence following discontinuation of highly active antiretroviral therapy (HAART), researchers have reported. Dr Tae-Wook Chun and colleagues (National Institute of Allergy and Infectious Diseases, Maryland, US) report two patients who had no detectable viral infection in resting CD4 cells, lymph nodes or peripheral blood while receiving HAART. Within weeks of discontinuation of therapy, a re-emergence of HIV was seen in both patients. The speed of re-emergence was similar to that of the establishment of initial infection (Nature 1999;401:874).