The objective of this study was to analyze the role of some trace metals in the immune system of nonallergic or atopic men. One of these elements (Zn) is essential for immune function, whereas others, present in the urban environment, are known to be allergenic (Ni and Cr) or toxic (Pb). Serum levels of interleukin (IL) 2, 4, 5, and 13 and of interferon-y and immunoglobulins, blood lymphocyte subsets, blood concentrations of Pb and Zn, serum levels of Zn, and urinary Cr and Ni concentrations were determined in 17 nonallergic men (mean age 34 years) and 17 healthy nonsymptomatic atopic men living in urban areas. The mean blood concentration of Pb (a marker of exposure to toxic agents) was 11 microg/dl in both groups, which showed similar levels of blood Zn and of urinary Ni and Cr, whereas the serum Zn concentration was lower in the atopic group. Serum IgE levels were much higher in atopic men than in nonallergics, whereas serum IL-2, IL-5, and IL-13 concentrations were lower, possibly due to binding to tissue receptors and cells. Moreover, in atopic subjects, numbers of blood CD4+-CD45RO-"virgin" lymphocytes were significantly lower and the CD4+ -CD45RO+/CD4+ -CD45RO- ratio was more elevated, indicating an activation of the immune system. Serum IgE levels of atopic men, in contrast to those of nonallergic subjects, were correlated with CD19+ and CD5--CD19+ B lymphocytes. Blood Pb levels of both groups of men were correlated with CD4+, CD4+-CD45RO+, and HLA-DR+ [activated T-, B-, CO4+ -C. and natural killer (NK) cells] lymphocytes; in particular, blood Pb levels of the nonallergic men were also significantly correlated with CD25+ cells activated by IL-2, whereas those of the atopic men were also correlated with CD3--HLA-DR+ (B- and NK-cells) and CD5--CD19+ lymphocytes. Besides serum Zn levels, urinary Ni and Cr of nonallergic men were correlated with several immune parameters; in particular, urinary Cr was correlated with serum IL-5 and IgE and urinary Ni was correlated with CD4+ -CD45RO+ and CD3+ -CD25+ lymphocytes. This correlation of Ni and Cr, also found in previous studies in nonallergic subjects, confirms the hypothesis that these metals are involved in mechanisms of immune response regulation and that allergy to Ni or Cr represents an alteration of physiological mechanisms. Previous experimental studies have demonstrated that Pb exerts immunomodulatory effects on CD4+ and B- lymphocytes, enhancing the production of Th2-like cytokines and IgE. These experimental results confirm those of this study, showing in atopic men the correlation of B-lymphocytes with both blood Pb and serum IgE levels. This suggests that Pb may enhance the incidence of atopy in populations exposed to an urban environment.