Macrophages were obtained from human peripheral blood by incubating mononuclear cells in plastic tissue culture flasks. After 1—14 days, the cells were used in mixed lymphocyte macrophage cultures. Macrophages could not, themselves, be stimulated to proliferation by allogenic cells, but stimulated allogenic lymphocytes. By the use of responding cells and stimulating macrophages from HLA‐D homozygous individuals, the HLA‐D determinants could be shown to be responsible for the stimulation of allogenic lymphocytes.