The ski/sno protooncogenes encode nuclear proteins that may act as transcription factors. We examined ski and sno mRNA expression in hemolymphopoietic lineages. The ski protooncogene is expressed in B- and T-lineage cells, mature macrophages, and mast cells. In normal murine marrow-derived progenitors analyzed by single-cell reverse transcription-polymerase chain reaction (RT-PCR), ski expression is limited to dual-lineage megakaryocyte/erythrocyte colony-starts. Expression of sno is more limited than ski in mature cells; it is expressed in T lymphopoietic cells, but not in B-lineage cells. The sno protooncogene is expressed more widely than ski in myeloid progenitors, as it is found consistently in tri-, dual-, and single-lineage progenitors. Both ski and sno are cell cycle-regulated in synchronized factor-dependent mouse myeloid cells. Expression of ski mRNA peaks in mid G1 in cells synchronized by isoleucine deprivation in the presence of growth factor, but falls off rapidly when growth factor is withdrawn. Expression of sno mRNA is maximal in early to mid G1 and then oscillates as the cells continue through cycle. These results suggest that the ski/sno protooncogenes play a role in hematopoiesis, growth factor responses, and cell cycle-regulation, with the two members of the family showing differing properties.