The tetrapeptide AcSDKP (Ser-Asp-Lys-Pro) is a reversible inhibitor of normal human hematopoietic progenitor growth. In this paper, we report that preincubation of bone-marrow mononuclear cells (MNC) with AcSDKP at 10(-10) M for 20 hours protects the granulocyte-macrophage colony-forming unit (CFU-GM) progenitors against photofrin II-mediated phototherapy. This protective effect was observed after short-term exposure to photofrin (2.5 micrograms/mL) and irradiation by high-energy doses at 514 nm. Nevertheless, AcSD-KP, which has no effect on leukemic cell proliferation, does not protect the HL-60 and K-562 leukemic cell lines against photosensitization.