We analyzed the differentiation of hemopoietic colonies derived from human paired daughter cells. Candidate progenitor cells were isolated by use of a micromanipulation technique from cultures of My-10 antigen- positive cord blood cells. Then nine to 36 hours later, the paired daughter cells were separated with a micromanipulator and allowed to form colonies in methylcellulose medium containing erythropoietin, phytohemagglutinin leukocyte-conditioned medium, and platelet-poor plasma. The cellular composition of the colonies was determined by differentiating all of the cells of the May-Grunwald-Giemsa-stained preparation. Of a total of 75 evaluable pairs of colonies, 35 consisted of 28 types of disparate pairs revealing nonhomologous lineage combinations. Forty pairs were homologous in lineage expression. However, the proportions of the individual cell lineages were significantly different in the members of some of the homologous pairs. Some pairs revealed significant differences in colony size. These observations are similar to those reported for murine paired progenitors and are consistent with the stochastic model of human stem cell differentiation.