The relationship between the presence of Ia-like antigens on human CFU-GEMM and BFU-E, and their responsiveness to the regulatory effects of AIF and PGE have been studied using normal human bone marrow cells. In primary methylcellulose culture the addition of 10(-6)-10(-9) M PGE1 results in the enhancement of the total number of BFU-E detected, with no observed effect on the number of CFU-GEMM. Addition of acidic isoferritins to primary cultures results in an approximately 50% inhibition of both BFU-E and CFU-GEMM proliferation. Removal of Ia+ cells by cytotoxic treatment with monoclonal antihuman HLA-DR (Ia) antibody plus C' resulted in: (a) reduction of total CFU-GEMM and BFU-E by approximately 50%, (b) abrogation of the enhancing effect of PGE on BFU-E, and (c) detection of populations of CFU-GEMM and BFU-E that are no longer sensitive to inhibition by AIF. Culture of marrow cells in suspension culture at 37 degrees C for 24 h prior to methylcellulose culture resulted in the loss of detectable Ia antigen on BFU-E and CFU-GEMM, loss of their responsiveness to AIF, loss of the enhancing effect of PGE on BFU-E, and the inability to detect cycling cells. Exposure of marrow cells to PGE, however, during the suspension phase augmented the total number of BFU-E, and CFU-GEMM detected and resulted in the detection of S-phase cells, expression of Ia antigens of both BFU-E and CFU-GEMM, and restoration of the ability to detect BFU-E and CFU-GEMM sensitivity to inhibition by AIF. After suspension culture with PGE, no further enhancement of BFU-E by PGE was observed. These results indicate that the expression of Ia antigens is important in the regulation of BFU-E and CFU-GEMM proliferation and add further evidence for a role for PGE in controlling progenitor cell Ia-antigen expression, cell cycle and, as a consequence, their proliferative capacity.