Compliance with antiretroviral therapy for HIV infection is a key factor in preventing the development of viral resistance. In children, the taste or unavailability of suspensions, the size of the pills, and the dosing frequency make compliance difficult. In certain patient populations, caregivers are aware of the importance of strict compliance yet have difficulty delivering medications. The placement of a gastrostomy (GT) feeding tube may be of help in assuring that the medications are given on time and in the proper amount. Here we present 4 patients, at 2, 3, 4 and 6 years of age who were failing antiretroviral therapy and in whom delivery of medication was difficult; a GT tube was electively placed to deliver their medications with simultaneous change of therapy to ≥ 3 drug regimens containing protease inhibitors. GT tube placement was well accepted by the children and parents, was successful in ensuring compliance, and resulted in no complications. In 2 patients, the GT tube was also used as a means of nutritional support. Eight to 12 weeks following GT tube placement and initiation of potent antiretroviral therapy, the HIV RNA fell to < 400 copies/ml in 3 children and from 108,000 to 1,362 copies/ml in the remaining child. CD4 lymphocyte counts rose a medium of 147 cells. In one child receiving antiretrovirals through a GT tube for 16 months, the HIV RNA has remained < 400 copies/ml with a CD4 cell rise from 8 to 902 cells/ml. Gastrostomy tube placement is an invasive procedure requiring anesthesia; however, achieving adequate medication delivery, proper dosing, and fluid delivery are important benefits in children with advanced HIV disease.