Previous reports have shown that interleukin 1 (IL-1) has radioprotective effects when given to mice 20 h before a lethal dose of irradiation and enhances granulocyte recovery in mice treated with cyclophosphamide. We have recently reported that IL-1 can provide protection for human bone marrow colony-forming cells including blast colony-forming cells (B1-CFC) treated with high doses of 4-hydroperoxycyclophosphamide (4-HC). In view of the recent reports that IL-1 induces interleukin 6 (IL-6) in fibroblasts and macrophages and that IL-6 and interleukin 3 (IL-3) are the main growth factors for B1-CFC, we have examined the ability of these interleukins to protect early human hematopoietic progenitor cells from the cytotoxic effects of 4-HC. In addition, we have also studied the ability of IL-3 to promote colony formation by 4-HC-treated bone marrow cells with or without IL-1 preincubation. In this study, we report that preincubation of bone marrow mononuclear cells with IL-3 or IL-6 prior to 4-HC results in no protection and, in fact, may be detrimental to early hematopoietic progenitor cells. On the other hand, addition of IL-3 to 5637-conditioned medium and erythropoietin enhanced colony formation by early progenitors following 4-HC treatment. These findings suggest that IL-3 and IL-6 are not responsible for the protection of early progenitor cells from 4-HC seen with IL-1, but that IL-3 does promote colony formation following 4-HC treatment.