In a collaborative cytogenetic analysis of blast cells from 638 children with acute myeloid leukemia, 74 (11.6%) of the patients had the typical t(8;21)(q22;q22), while seven (1.1%) had complex variant translocations also involving 8q22 and 21q22 as well as a variable chromosome. In each case with a complex rearrangement, the myeloid leukemic cells contained Auer rods and were classified as M2 in the French-American-British (FAB) system. These seven children had a median age of 14 years (range, 7.3-18.9 years), a median initial leukocyte count of 9.1 x 10(9)/L (range, 2.5-142.2 x 10(9)/L), and have survived leukemia free for a median of 23 months (1-41 months) after attaining complete remission. The variable chromosomes in these seven cases--1, 2, 7, 12, 13, 15, and 17--appeared to be randomly involved. The clinico-biologic features of our cases with a variant t(8;21) are consistent with those of the published cases with the standard t(8;21), and support the hypothesis that the critical genetic alteration produced by the t(8;21) is located on the derivative 8.