These studies were undertaken to examine the in vitro effects of the cysteine pro-drug L-2-oxothiazolidine-4-carboxylic acid (Procysteine) on human immunodeficiency virus expression. Procysteine inhibited HIV expression in human peripheral blood mononuclear cells as detected by measurement of supernatant core antigen. In transient transfection assays, Procysteine inhibited gene expression controlled by the HIV-1 promoter in activated Jurkat cells but not in resting Jurkat cells. Gel-shift assays showed that Procysteine inhibited NF-kappa B DNA binding activity in nuclear extracts. Procysteine did not affect the production of interleukin-2 by peripheral blood mononuclear cells of healthy HIV-seronegative subjects, as measured by bioassay but it decreased the density of cell-surface interleukin-2 receptors detected by flow cytometry after stimulation with phytohemagglutinin (PHA). Thus, Procysteine inhibits HIV expression, HIV promoter activity, and NF-kappa B binding activity in vitro. Procysteine does not affect interleukin-2 production but inhibits interleukin-2 receptor expression in PHA-stimulated peripheral blood mononuclear cells.