This study describes the frequency of monoclonal gammopathy of undetermined significance (MGUS) and the changes in some inflammation-related serum proteins in 157 patients with nonimmune chronic idiopathic neutropenia syndrome (NI-CINS). Of these patients, 42 had pronounced neutropenia with neutrophil counts < 1500/microL, and 115 had mild neutropenia with neutrophil counts ranging from 1500 to 2499/microL. Sixty-six volunteers served as healthy control subjects and 157 age- and sex-matched patients hospitalized for nonmalignant diseases served as patient control subjects. We found that 28.6% of patients with pronounced neutropenia and 14.8% of patients with mild neutropenia had increased serum gamma globulins (above the 95% confidence limit of values of the control subjects). In the group of patients with pronounced neutropenia, 30.9% had increased immunoglobulin (Ig)G values and 23.8% had increased IgA values. In the group of patients with mild neutropenia, 17.4% had increased IgG values and 21.7% had increased IgA values. IgG and IgA values strongly correlated with the neutrophil count. No changes in serum IgM were found. Three of 42 patients with pronounced neutropenia (7.14%) and 3 of 115 patients with mild neutropenia (2.61%) had serum immunofixation tests which showed a small monoclonal spike--4 were IgG-kappa type, 1 was IgG-lambda type, and 1 was IgA-kappa type. None of the healthy or patient control subjects had any evidence of MGUS. No significant changes in the amount of monoclonal spikes were documented during an 18- to 143-month follow-up (median, 58 months). Except for significantly increased alpha1-antitrypsin levels, there were no significant differences in the levels of acute-phase proteins studied between the study patients and the control subjects. These findings are consistent with our previous report suggesting the possible existence of an unrecognized low-grade chronic inflammation in patients with NI-CINS, which may be involved in the pathogenesis of neutropenia in the affected subjects.