Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may occur in association with a monoclonal gammopathy of undetermined significance (MGUS) or a variety of other systemic illnesses. It is not known if the clinical features of CIDP are altered by the presence of an MGUS. We compared demographic features, clinical presentation, improvement and outcome after initial treatment, and electrodiagnostic features of a group of 77 patients with idiopathic CIDP (CIDP-I, no associated systemic illness) with 26 patients with CIDP in whom an MGUS was found during evaluation of the neuropathy (CIDP-MGUS). Patients with CIDP-MGUS had, on average, a more indolent course and less severe weakness than patients with CIDP-I, despite similar motor conduction studies. CIDP-MGUS patients also demonstrated less functional impairment, more frequent sensory loss, and more abnormal sensory conduction studies than patients with CIDP-I. Because of the greater improvement of CIDP-I patients with treatment, both groups had similar outcomes from their initial episodes of weakness. Subgroup analysis of CIDP-MGUS patients did not demonstrate differences between groups with IgM and IgG or IgA gammopathies.