Glucocorticosteroids (GCS) are in vitro polyclonal activators of immunoglobulin (Ig) production for human mononuclear cells (MC) from virtually all adult donors. However, GCS treatment of cord blood MC resulted in Ig production in only 12/41 samples. This GCS effect is T cell and monocyte dependent and is mediated in part by a soluble T cell replacing factor. The inconsistent response of cord MC could be due to either cellular or soluble factor differences from adults. In 11/12 samples tested, irradiated cord T cells did help adult B cells, but less than did irradiated allogeneic adult T cells. T cell suppression in cord samples is unlikely inasmuch as higher cord T cell numbers and proportions increased the number of responding cord samples. Cord monocytes function adequately, because monocytes supported GCS responses when cord non-T cells had sufficient T cell help. The T cell replacing factor was found in supernatants of unstimulated cord as well as in adult MC cultures, but was less than 50% as potent. Cord B cells did not develop GCS-induced Ig production with such supernatants, suggesting that cord B cells may require a higher concentration or more prolonged exposure to T cell help. With a 2:1 ratio of irradiated adult T cells to cord non-T cells, only 25% of cord samples responded to GCS (compared to greater than 95% of adult samples), but with a ratio of 4:1, 75% responded. IgM was the predominant isotype secreted by GCS-stimulated cord cells, but 6/14 samples also produced IgG and 8/14 produced IgA. Thus, the functional immaturity of both cord T and B cells exists for GCS-induced Ig production, but with appropriate conditions GCS can activate most samples of cord B cells to synthesize Ig.