Our original studies of the enkephalins were centered on behavioral stress and brain dopaminergic interactions. More recently we discovered the enkephalins to be immunomodulators as evidenced by their enhancement effects on lymphocyte blastogenesis in mice, increases in the sizes of the thymus or spleen in rodents, and prolongation of survival of BDF1 mice inoculated with attentuated L1210 cells. Finally, in studies of human blood samples from both normal volunteers and cancer patients, the enkephalins were demonstrated to stimulate active T cell rosettes and natural killer cell activities (in vitro). These studies support our hypothesis that, in stress, the enkephalins modulate the effects of steroid hormones on the immune system.