Intravenous injection of killed Bordetella pertussis caused a tremendous increase in peripheral blood lymphocytes and a lesser increase of nucleated cells in the spleen. The pertussis-treated peripheral blood leukocytes had increased responsiveness to phytohemagglutinin PHA, but no increased graft-vs.-host (GvH) reactivity. In contrast, pertussis-treated nucleated spleen cells had unchanged responsiveness to PHA, but had showed a slight increase in GvH reactivity. These results are best explained by heterogeneity of thymus-derived cells with regard to their functional abilities (response to PHA or GvH initiation) and a differential effect of pertussis vaccine on subpopulations of thymus-derived lymphocytes.