This project has focussed on studying the ability of human immunodeficiency virus (HIV) to infect various human and mouse cell lines. The CD4 gene which encodes an important receptor for HIV infection was expressed in human and mouse cells and susceptibility of these cells to HIV infection was followed using a sensitive focal immunoassay (FIA) technique. The results indicated that HIV infection in certain human cells (HeLa) was related to the level of CD4 expression in different clones. However, in other human lines such as U87 astroglioma and SCL1 squamous cell carcinoma HIV infection was only rarely successful in spite of very high CD4 expression. Further studies indicated that HIV could bind to the CD4 on these cells, but HIV did not undergo successful fusion and entry of the cells. These results suggested that other cellular molecules in addition to CD4 were required for HIV entry of cells. This possibility was confirmed by showing that HIV could infect these human cells when the usual HIV entry mechanisms were bypassed by using viral DNA to tranfect the cells or by infecting with HIV genomes pseudotyped by packaging in envelope proteins of mouse retroviruses which use receptors other than CD4 for entry. Similar experiments were also carried out using mouse cell lines expressing human CD4. In these mouse cells, there were at least two levels of resistance to HIV infection. The first was a block in entry similar to U87 and SCL1 human cells, but even when this block was bypassed by transfection or viral pseudotyping, mouse cells still had a markedly reduced level of HIV infection. Present data suggests that the reduced HIV expression in transfected mouse cells may be due to poor functioning of HIV promotor and enhancer sequences in these mouse cell cultures.