In 12 myeloma patients responding to chemotherapy (7 IgG and 5 IgA), we studied the effect on the anion gap of a 50% reduction in the serum paraprotein concentration. In contrast to the pretreatment anion gap which was decreased in IgG myeloma and increased in IgA myeloma, the value calculated when the paraprotein spike was halved showed a tendency towards normalization in the former type of myeloma, whereas it appeared as quite normalized in the latter. Our results lend further support to the conceptions that IgG and IgA paraproteins behave in the serum as cations and anions, respectively, and that serial determinations of the anion gap may be of value for monitoring the response to treatment in patients with multiple myeloma.