To investigate the prognostic significance of gammaglobulin and immunoglobulin levels in chronic lymphocytic leukemia (CLL), survival studies were performed in a series of patients with that disorder. The survival probability of patients with initial levels of gammaglobulin of less than 700 mg/dl was significantly lower (P = 0.03) than in patients with initial levels of 700 mg/dl or more. Decreased initial levels of IgG and IgA also were associated with reduced survival probability (P = 0.027 and P = 0.014, respectively), whereas hypo-IgM did not show any influence on survival. When the influence on survival of gammaglobulin and immunoglobulin concentration was analyzed by Cox's multivariate model, the only variable which entered the regression at significant level was IgA (P = 0.006). As shown by the same type of analysis, the prognostic value of hypo-IgA is independent from the clinical staging. The natural history of hypogammaglobulinemia and hypoimmunoglobulinemia was investigated by sequential analysis in a series of untreated patients. The appearance of decreased levels of these globulins was found to be a continuous process developing spontaneously during the untreated course of the disease. Among factors associated with the appearance of hypogammaglobulinemia during the evolution of CLL, initial lower levels of IgG and IgA, but not IgM, were found in a multivariate analysis.