The aim of this project was to determine whether therapeutic drug monitoring (TDM) and subsequent dose modification is effective in the management of protease inhibitor (PI)-associated toxicity. A retrospective case-notes review of patients who had had TDM for suspected antiretroviral drug toxicity from November 2000 to March 2002 was carried out. This identified six symptomatic patients in whom high plasma drug levels of a PI had been found and subsequent dose modification was associated with improvement/resolution of symptoms. In 5/6 patients viral loads were below the level of detection prior to TDM and remained so after dose reduction of PI. TDM-directed dose modification of PI enables patients to continue effective regimens of highly active antiretroviral therapy, thus avoiding the need to switch the regimen.