New guidelines suggest that HIV-infected pregnant women should be offered combination antiretroviral therapy (zidovudine and protease inhibitors) to prevent fetal HIV infection but concerns remain about potential adverse effects for the infant. Prior small case series have suggested an increased risk for hemangioma. In this study we used zidovudine and indinavir, alone or in combination, to assess the effect on an in vitro angiogenesis system for endothelial cells. The increase in capillary tube formation, was associated with a significant increase in vascular endothelial growth factor (VEGF) production. Zidovudine and indinavir used in combination do not further strengthen both endothelial cell tubes formation and VEGF secretion. We conclude that zidovudine and indinavir may induce angiogenesis in an in vitro model.