Serum amyloid A protein (SAA) was extracted from serum using hydrophobic interaction chromatography and four or six isoforms were separated by isoelectric-focusing. These represented three pairs of isoforms, each with and without an N-terminal arginine. SAA1 (pI 6.1), SAA1 des-arg (pI 5.9), SAA2 alpha (pI 6.9) and SAA2 alpha des-arg (pI 6.6) were found to be present in all individuals from Europe and the USA. A minority of these individuals (11 of 56) expressed SAA2 beta (pI 7.1) and SAA2 beta des-arg (pI 6.8). Serum from patients in Papua New Guinea and Malawi both showed a much higher frequency of SAA2 beta. There was no indication of altered isoforms in regions with high incidence of reactive AA amyloidosis. In sequential serum samples, concentrations of des-arg isoforms were found to reach a maximum 0-24 h later than isoforms with an arginine. Concentrations of the isoform SAA1 decreased faster in five of six patients (16 +/- 7.5 h to decrease 50%) than SAA1 des-arg (22 +/- 11 h to decrease 50%). Variations in the handling of N-terminal arginine may be important for the formation-susceptibility of amyloid deposits.