We have investigated several aspects of nonspecific immunity in Down syndrome (DS), utilizing peripheral polymorphonuclear leukocytes (PMNL), obtained from 12 children aged 8-16, diagnosed as trisomy 21, and their healthy matched controls. We used the under agarose method for chemotaxis assays, and flow cytometry for the determination of phagocytosis of monodispersed fluorescent beads, metabolic burst activity, and neutrophil surface marker expression on these cells. Our results indicate that a chemotactic defect exists in PMNL of DS children. However, no statistically significant differences were found between PMNL from DS children and those from controls in phagocytosis, oxidative burst, and expression of the markers CD11a, CD11b, CD16, and CD 18. Furthermore, no overexpression of CD11a and CD18 was present as a consequence of gene overdosage in PMNL from DS children. On the other hand, 3 different neutrophil subpopulations could be observed according to the CD16 staining pattern in DS children and controls; this might be a consequence of genetic variation or may represent different states of activation of these cells. Other factors such as T-cell involvement, and the role of cytokines, cyclic nucleotides, and zinc serum levels in DS patients should be further investigated in order to define the causes of the immunological derangement present in this condition.