Inv(16)(p13q22) and t(16;16)(p13;q22) are recurring chromosomal rearrangements which juxtapose the metallothionein gene cluster at 16q22 with other DNA sequences from 16p13. We have studied 20 men and 13 women who had acute nonlymphocytic leukemia; 27 patients had an inv(16) and six patients had a t(16;16). Eight patients also had trisomy 22, and four had trisomy 8. All but two patients had the unique morphologic features of acute myelomonocytic leukemia with abnormal eosinophils (M4Eo). In one patient with M4 leukemia, abnormal eosinophils were not observed in the marrow. A second patient had acute monocytic leukemia, plus abnormal eosinophils. Eosinophils constituted 1% to 46% (median, 6%) of the bone marrow cells, and in all but a single patient, the eosinophils exhibited distinctly abnormal morphology. Twenty-five patients have had a complete remission (78% of treated patients). Nine patients have remained in remission longer than 24 months. No patient had symptoms of central nervous system (CNS) disease at diagnosis, and none had CNS leukemic mass lesions at any time. Treatment with high-dose cytarabine may have provided prophylactic CNS therapy. Four additional patients with chromosomal rearrangements involving a breakpoint at 16q22 but not at 16p13 have had different morphological features and different clinical courses. Thus, the juxtaposition of genes at 16p13 and 16q22, which occurs both in the inv(16) and the t(16;16), results in a specific subset of acute nonlymphocytic leukemia that has a favorable prognosis.