During a period of 9 years, we performed immunological marker analysis in 164 children with acute lymphoblastic leukemia. In four children the diagnosis acute leukemia could not be established by cytomorphological analysis of bone marrow and peripheral blood samples at initial presentation. In two of these four children a hypoplastic bone marrow was found, whereas the bone marrow of the other two children was normocellular. Using double immunological marker analysis, we detected high frequencies of CD10+, TdT+ cells in bone marrow (range: 18-53%) as well as peripheral blood (range: 0.04-19.5%). In control bone marrow and peripheral blood samples from healthy children, the frequency of CD10+, TdT+ cells does not exceed 10% and 0.03%, respectively. Based on the immunological data, a common acute lymphoblastic leukemia (ALL) was suspected. In addition, chromosome analysis revealed a high hyperdiploid (> 50 chromosomes) karyotype in three patients and t(9;22) in one patient. At 18 to 68 days after initial presentation, an ALL was diagnosed according to cytomorphological criteria in all four patients. At that time the percentage of CD10+, TdT+ cells in bone marrow and peripheral blood had increased significantly. One patient could be monitored frequently from initial presentation onwards. First a decline in the percentage of CD10+, TdT+ cells was found, although treatment consisted only of red blood cell transfusion and antibiotics. Subsequently the percentage of CD10+, TdT+ cells gradually increased until the morphological ALL diagnosis. These results illustrate that CD10, TdT double immunological marker analysis is a useful tool for early diagnosis of smoldering ALL in patients with a suspicious bone marrow, even when the bone marrow is hypoplastic.