To investigate the influence of race, cigarette smoking, and immunologic parameters on serum immunoglobulins, we analyzed serum IgG, IgA, and IgM levels in 455 healthy adults. The study population ranged in age from 20 to 69 years, including 282 whites and 173 blacks, 181 never-smokers, 93 ex-smokers, and 181 current smokers. Race and smoking were independently associated with alterations in serum IgG levels. Blacks had significantly higher IgG levels than whites (1,587 vs. 1,209 mg/dl; P < 0.001), and never smokers had significantly higher levels than current smokers (1,426 vs. 1,287 vs. mg/dl; P < 0.001). IgA and IgM levels were unrelated to race or smoking. Serum IgG was also found to be directly related to the proportion of HLA-DR+ cells and the level of soluble interleukin-2 receptors (sIL-2R) and inversely related to the proportion of CD4+ cells. Investigation of this racial heterogeneity may provide insights into the pathogenesis of immunologic diseases that exhibit unexplained racial variation.