It is still difficult to clinically distinguish Philadelphia (Ph1)-positive acute lymphoblastic leukaemia (ALL) from Ph1-positive chronic myelogenous leukaemia (CML) in lymphoid crisis. In this study we tried to discriminate between these two disorders by simultaneous analyses of cell morphology and karyotype in single in vitro colonies. We studied three patients with Ph1-positive ALL and four with Ph1-positive CML in various phases of the disease. Bone marrow and peripheral blood cells obtained directly from all seven patients showed abnormal karyotypes including Ph1-chromosomes. Normal karyotypes were found in a small proportion of cells from two ALL patients, but none were found in any from the CML patients. The patients' mononuclear cells (MNCs) were plated at 1-5 x 10(4)/ml in semi-solid medium containing methylcellulose plus phytohaemagglutinin-stimulated leucocyte conditioned medium and erythropoietin. After 9-14 d cultivation, granulocyte-macrophage, erythroid and mixed colonies obtained were used for simultaneous analysis of cell morphology and karyotype. Morphological examination showed that these colonies contained neutrophils, eosinophils, basophils, macrophages and/or erythroblasts in various combinations. No lymphoblast colonies were obtained under the culture conditions used. Cytogenetic examination revealed that all metaphase cells observed in colonies obtained from Ph1-positive ALL patient MNCs had a normal karyotype, whereas those in colonies from Ph1-positive CML patient MNCs had abnormal karyotypes, including Ph1 chromosomes, suggesting that the difference between the two disorders involved a difference in cell lineage. Our results showed that this method was a practicable method for distinguishing Ph1-positive ALL from Ph1-positive CML in lymphoid crisis.