The variability in response of peripheral blood mononuclear cells (PBMC) from 95 healthy donors to pokeweed mitogen (PWM) was investigated. Age, sex, and blood group of the donors, the numbers of PBMC recovered from 500 ml blood, the percentage of monocytes therein, the presence of antilymphocyte antibodies (L-Cyt), or of anti-cytomegalovirus (CMV) antibodies, as well as HLA-B8 and HLA-DR4 were evaluated for their relation with the level of blast cell formation, proliferative response, and immunoglobulin G (IgG) synthesis, induced by PWM. The results showed that increasing age of the donors and the presence of anti-CMV antibodies are significantly associated with low proliferative responses of PBMC, whereas the HLA-B8 antigen and female donor sex were found to be associated with high blast cell formation after PWM stimulation. High percentages of monocytes in isolated PBMC at the onset of stimulation were inversely associated with IgG production, whereas the HLA-DR4 antigen was associated with high levels of IgG production, induced by PWM. The observed relations indicate that for comparison of responses of unseparated PBMC to PWM between patients and healthy controls, age, sex, and laboratory data, including the HLA background of donors, may have to be taken into account.