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To determine the rate of plasma HIV-1 RNA rebound in patients stopping highly active antiretroviral therapy (HAART) after achieving undetectable viral load.Sequential plasma HIV RNA levels were measured in six patients during the 21 days following withdrawal from HAART. Plasma samples were obtained from six patients who chose to withdraw from HAART because of lipodystrophy, narcotic overdose, insomnia and/or high blood pressure. Longitudinal plasma viral load was determined in triplicate upon stopping therapy.All patients had plasma viral loads below 50 HIV RNA copies/ml at the time of stopping therapy and had had levels below 500copies/ml for a median of 390 days (range 39-542 days). Plasma HIV rebound upon stopping therapy was rapid (median increase 0.2 log/day; range 0.15-0.42 log/day) and initially appeared to follow first-order kinetics. Plasma HIV RNA levels returned to greater than 500copies/ml within 6 to 15 days (median 10 days) and approached or exceeded pre-therapy levels in all patients within 21 days of stopping therapy. Extrapolating backwards to the time at which individuals stopped therapy suggested that patients had tens of thousands of total body plasma HIV RNA copies despite having ‚undetectable‚ plasma HIV RNA.HIV RNA in plasma rebounds within days of stopping antiretroviral therapy. A considerable burden of total body plasma HIV RNA likely remains even during effective HAART therapy.