Swainsonine, an inhibitor of mannosidase II, involved in N-linked glycoprotein processing, modifies expression of cell surface receptors. This alkaloid has strong anti-metastatic and immunomodulatory activity; it enhances stimulation of lymphocytes triggered by concanavalin A (ConA) but suppresses stimulatory effects of phytohaemagglutinin (PHA). We presently observe that swainsonine decreases expression of the interleukin-2 (IL-2) receptor (IL-2R) on PHA-stimulated human peripheral blood lymphocytes, measured by binding of a monoclonal antibody that recognizes the 55-kD glycoprotein subunit (alpha) of this receptor. Proliferation of the PHA-stimulated lymphocytes is suppressed by swainsonine, which manifests in the decreased proportion of both cells entering G1 (from G0) and those progressing through S. G2 and M. This suppression can be overcome by addition of IL-2 into cultures. In contrast, swainsonine has no effect on IL-2R expression and stimulation (cell cycle progression) of lymphocytes triggered by the monoclonal antibody OKT3. The data suggest a possibility that the observed swainsonine effects on lymphocytes stimulated by PHA are mediated via surface receptors other than IL-2R. These receptors may appear prior to IL-2R and be also involved in cell stimulation by PHA but not by other mitogens.