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Erythema nodosum leprosum (ENL) is a serious complication of lepromatous (L) disease in leprosy. We have previously shown that of the four IgG subclasses, IgGl and IgG3 Mycobacterium leprae-specific antibodies are significantly lower in leprosy patients during ENL reaction compared with untreated L patients. To see if this decrease results from a down-regulation of antibody synthesis during ENL, the frequency of antibody-secreting B cells (ABSC) in the blood compartment was determined by ELISPOT and related to serum immunoglobulin concentrations (μg/ABSC). Control groups consisted of 16 patients with stable L disease and 32 healthy endemic controls (EC). Paired samples were analysed during acute ENLS (n=13) and after the reaction had subsided to identify changes associated with ENL. Polyclonal (PC) IgGl was elevated in L patients compared with EC (325μg versus 180 μg). Interestingly, patients during acute ENL showed concentrations higher than L patients (419μg), which decreased after the reaction had subsided (260μg), indicating the transient nature of the antibody response. IgG2 antibodies showed the reverse trend and were lower during ENL and increased after the reaction had subsided. The mean concentrations for PC IgG3 and IgG4 antibodies were similar during ENL and after the reaction had subsided. Thus, decrease in M. leprae-specific IgGl and IgG3 antibodies is not related to down-regulation of B cell responses. Identification of factors which regulate PC IgGl antibody synthesis may provide additional insights into determinants of ENL reactions. [ABSTRACT FROM AUTHOR]