To investigate some aspects of immune function in cystic fibrosis, we measured serum immunoglobulins in 419 patients. Twenty-two per cent of the 154 patients less than 10 years old had hypogammaglobulinemia-G, whereas the older patients had normal or elevated serum immunoglobulins. A single mechanism accounting for the extraordinary prevalence of hypogammaglobulinemia in young patients with cystic fibrosis was not defined in studies of T and B-lymphocyte function in vitro or in studies of IgG metabolism in vivo. Analysis of objective clinical data, including arterial blood gases, chest roentgenograms, and bacteriologic cultures, indicated that the patients with hypogammaglobulinemia had significantly less severe lung disease than did age-matched patients with cystic fibrosis and normal or elevated IgG levels. We conclude that progression of lung disease may be due in part to a hyper-immune response.