Monoclonal gammopathy of undetermined significance (MGUS) of the immunoglobulin M (IgM) class was diagnosed at our institution in 213 patients who resided in the 11 counties of southeastern Minnesota from 1960 to 1994. The median age at diagnosis was 74 years and the median concentration of serum M-protein was 1.2 g/dL. The 213 patients were monitored for 1567 person-years (median, 6.3 years), during which 71% died. During follow-up, non-Hodgkin's lymphoma (n = 17), Waldenstrom's macroglobulinemia (n = 6), primary amyloidosis (n = 3), and chronic lymphocytic leukemia (n = 3) developed in 29 patients (14%). The number of patients with progression to lymphoid neoplasms was 15.9 times that expected in the general population. The cumulative probabilities of progression to one of these disorders were 10% at 5 years, 18% at 10 years, and 24% at 15 years. The overall average risks for progression were approximately 1.5% per year. Rates of death resulting from other diseases (cardiovascular, cerebrovascular, etc.) were 31% at 5 years, 52% at 10 years, and 65% at 15 years. Multivariate analysis revealed that only the concentration of serum M-protein at diagnosis and the serum albumin value were independent predictors of progression. It was concluded that the patients with IgM MGUS should be followed indefinitely.