Polyspecific IgG given intravenously at high dose (IVIG) are increasingly used as an immunomodulating therapy in autoimmune diseases. However, very few studies have dealt with the action of IVIG on the expression of the leukocyte markers. During a clinical trial in which 13 young and healthy women received IVIG to prevent unexplained recurrent abortions we have evaluated by flow cytometry the action of IVIG on 17 clusters of leukocyte differentiation (CD). We found that the IVIG perfusions (0.5 g/kg) induced an increase in the number of polymorphonuclear and monocyte cells in the peripheral blood. This effect lasted 8 days. The IVIG treatment had no effect upon T cell populations stained with antibodies specific for CD2, CD3, CD4, CD8 and on CD4(+)CD45RA(+), CD4(+)CD29(+), CD8(+)CD28(+), CD8(+)CD28(-) subpopulations. A weak decrease in the B cell number was observed. The most striking phenomenon was the decrease in the number of CD56(+) cells, whereas CD16(+) and CD57(+) cells were unaltered. By the double-staining technique we showed that CD56(+)CD16(+) cells became CD56(-)CD16(+) cells. Moreover, IVIG decrease the expression level of the LFA-I molecule on monocytes and lymphocytes. The other adhesion molecules studied remained steady (CD11b, CD49d, CD49e, CD29, CD28, and CD62L). This study has shown that IVIG have no effect on 15 of 17 CD used but downmodulate two adhesion molecules playing a key role in the immune system. (C) 1994 Academic Press, Inc.