The in vitro culture growth of marrow granulocyte-macrophage progenitors (CFU-GM assay) was studied in 102 consecutive patients with newly diagnosed primary myelodysplastic syndrome (MDS) to determine its diagnostic utility and prognostic value. There were 18 patients with refractory anemia (RA), eight RA with ringed-sideroblast (RARS), 30 RA with excess of blasts (RAEB), 18 chronic myelomonocytic leukemia (CMML), and 28 RAEB in transformation (RAEB-T). Patients with MDS had a significantly lower number of GM colonies and a significantly higher cluster to colony ratio than those of normal controls and patients with cytopenias of other causes. Six in vitro growth patterns were observed; 85% of patients with MDS showed various abnormal growth patterns, and 42% of all MDS patients exhibited a leukemic growth pattern at diagnosis. None of the 40 patients with cytopenias of other causes had a leukemic type growth. A leukemic growth pattern was rarely observed in patients with RA and RARS (4%), but was common in other subgroups (57%). The distribution of various growth patterns was not statistically different among patients with RAEB, CMML, and RAEB-T. Thirty-six patients developed acute leukemia during the follow-up period. The MDS patients with leukemic type growth were at increased risk of rapid progression to acute leukemia, and they also had a shorter survival time than patients with a non-leukemic pattern. These results showed that simply scoring the number of CFU-GM is of limited value for the diagnosis and the prediction of prognosis of MDS, whereas the in vitro marrow culture growth pattern is of prognostic significance independently of the FAB classification. It is concluded that the in vitro growth pattern of marrow CFU-GM is helpful in diagnosing patients with MDS as well as in predicting their clinical outcome.