The initial step in the infection cycle of human immunodeficiency virus type 1 (HIV-1) involves binding of its surface glycoprotein gpl20 to the T lymphocyte CD4 antigen. CPF-DD is a low molecular weight inhibitor of HIV infectivity that inhibits gpl 20 binding to CD4 in vitro (Finberg et al, Science 249, 287-291, 1990). We find, however, that the actions of CPF-DD are not limited to its ability to interfere with gpl20-CD4 binding; its predominant action is to remove the viral envelope from the underlying core. Subsequently the virions disintegrate. Most enveloped viruses tested were inhibited by CPF-DD, but the infectivity of noneveloped viruses was unaffected or only slightly reduced.