As expected, the productive infection of several monocytic cell lines by HIV-1 led to a diminution of cell-surface CD4 antigen. However, unlike findings reported for HIV-1-infected T cells, this decrease was not accompanied by a similar reduction in levels of CD4 transcripts. OKT4 monoclonal antibodies (MAbs) to CD4 were used in immunoprecipitation experiments to show that intracellular CD4 levels were diminished in U-937 monocytic cells that had been infected by HIV-1. These MAbs also coprecipitated viral gp120, indicating that CD4-gp120 complexes are present in infected monocytes. Our results therefore demonstrate that cell-surface down-modulation of CD4 is exclusively a post-transcriptional event in HIV-1 infected monocytic cells. These data suggest that HIV-1-mediated depletion of cell-surface CD4 in monocytes does not involve transcript down-modulation as has been reported in T lymphocytes.