Leukemic cell chromosomal findings in 27 infants were analyzed. Among the 18 cases of acute nonlymphoblastic leukemia (ANLL), all but two were classified as monocytic or myelomonocytic. The remaining nine cases were acute lymphoblastic leukemia (ALL), seven lacking the common ALL antigen and two having cytoplasmic immunoglobulin (pre-B phenotype). Twenty-five cases (93%) had an abnormal karyotype, 21 (84%) being pseudodiploid. Chromosomal translocations were detected in 67% of the ANLL cases and in 78% of the ALL cases. Nonrandom chromosomal abnormalities included the t(9;11)(p21-22;q23) in three cases of monocytic leukemia, inversion of chromosome 16 in three cases of myelomonocytic leukemia with bone marrow eosinophilia, and t(4;11)(q21;q23) in one case of ALL. Chromosomal regions preferentially involved in infant leukemia included 11q23-25 (13 cases), 9p21-22 and 10p11-13. All but one of the 24 cases with chromosomal breakage or rearrangement had breakpoints that corresponded to known fragile sites, half of which were at 11q23-25, a finding that may have pathogenetic importance. The CALLA- or pre-B phenotype and the presence of chromosomal translocations in most infants with ALL provide a biological explanation for their poor prognosis.