Previous work suggests that gp120 mediates the passage of HIV-1 and infected immune cells across the blood-brain barrier (BBB) by induction of adsorptive endocytosis (AE) in brain endothelial cells. Other work has suggested that cytokines may increase the permeability of the BBB to free virus or infected immune cells. Here, we investigated the ability of lipopolysaccharide (LPS), a bacterial wall toxin that stimulates the release of cytokines, to increase gp120 passage across the BBB by enhancement of AE and/or induction of BBB disruption. We found that LPS enhanced the passage of gp120 radioactively labeled with 125I (I-gp120) in a reversible, time-dependent, prostaglandin-independent manner that was not completely explained by disruption of the BBB. LPS also enhanced wheatgerm agglutinin mediated uptake of I-gp120 almost exclusively through the potentiation of AE. These results show that LPS or cytokines released by LPS can have a major effect on the permeability of the BBB to HIV-1gp120 both by stimulating AE and by inducing a disruption of the BBB. This suggests that bacterial infection or other inflammatory states could facilitate invasion of the CNS by HIV-1.