We studied the mixed leukocyte culture suppression generated by cord and newborn mononuclear cells stimulated by concanavalin A (Con A) compared to normal adult cells and cells from patients with systemic lupus erythematosus. Also we studied the effect of supernatants from cord or adult cells stimulated with Con A linked to sepharose (Con A sepharose). Peripheral blood mononuclear cells from 15 adults, 10 normal newborns, 23 cord blood samples, and 11 patients with systemic lupus erythematosus were preincubated with Con A for 48 hr, irradiated, and added to a one-way mixed leukocyte culture. Adult Con A-activated cells suppressed the mixed leukocyte culture by 30 +/- 6.5%. By contrast cord cells and newborn cells had no suppressive activity; these cells resulted in stimulation of 18 +/- 12.1 and 18 +/- 7%, respectively. This lack of suppression also was present in systemic lupus erythematosus cells (11.2 +/- 13.3). The supernatants of both Con A sepharose-stimulated cord and adult cells showed significant suppressive activity and there was some suppressive activity of sepharose-stimulated cells alone. These results suggest that the mixed leukocyte cultures suppressive activity observed previously by newborn cells is radiosensitive and dependent on ongoing cell division for its expression. It also is independent of prior mitogenic stimulation.