The finding that eluted mesangial IgA and serum IgA from patients with IgA nephropathy had a restricted anionic charge contrasting with normal serum IgA prompted us to study the charge of the kappa and lambda subclasses of IgA. Serum IgA from 11 patients with IgA nephropathy and 11 controls was purified by affinity chromatography by binding to jacalin. The charges of IgA were studied by a novel method. The spectrotype of total IgA was first studied by isoelectric focusing and immunoblotting. IgA lambda and IgA kappa was further analyzed by reacting with specific monoclonal antibodies. The amount of IgA with different pIs was analyzed by computerized densitometry. The anionic:cationic (A:C) ratio of IgA using pI 5.6 as the dividing point was greater in patients (at clinical quiescence and during exacerbation) than in controls (1.67 +/- 0.31 versus 1.36 +/- 0.27, p < 0.025). IgA lambda in both groups was anionic (A:C ratio 2.22 +/- 0.77 versus 2.36 +/- 0.36) and IgA kappa was cationic (A:C ratio 1.15 +/- 0.36 versus 1.04 +/- 0.39) but no difference in the A:C ratio was demonstrated. The increased A:C ratio in total IgA in patients was due to raised serum IgA lambda (kappa/lambda ratio 1.11 +/- 0.14 in patients and 1.51 +/- 0.16 in controls, p < 0.01). We had previously shown a predominant mesangial deposition of IgA lambda in IgA nephropathy. Animal experiments have revealed the preferential mesangial deposition of immune complexes is related to their anionic charges. Our data of raised anionic IgA lambda in IgA nephropathy may be important in determining its selective mesangial binding that could contribute to the immunopathogenesis.