Successful long-term cultures were generated from marrow buffy-coat cells incubated with either of two monoclonal anti-Ia antibodies, 7.2 and HBIOa, and complement. The mean CFU-GM toxicity for 7.2 and HBIOa was 81% and 94%, respectively, of the complement control. Cultures generated from marrows treated with 7.2 and complement produced between 30% and 163% of the CFU-GM (mean, 78.2 +/- 52.4%) and 33% of the BFU-E produced by the complement control cultures. Long-term cultures from marrows treated with the more cytotoxic HBIOa antibody yielded 261% of the CFU-GM present at culture initiation. Our data suggest that the progenitor cells necessary for generation of long-term cultures from human marrow are Ia-negative and may represent less mature stem cells than those measurable by semisolid colony assays. Furthermore, marrow treated with cytotoxic anti-Ia antibodies may be suitable for use in autologous transplantation.