We evaluated the clinical usefulness of determinations of alpha 1-acid glycoprotein microheterogeneity patterns in distinguishing patients who have active systemic lupus erythematosus (SLE) from those who have SLE with intercurrent infection. We used agarose affinity electrophoresis with concanavalin A (Con A) as a ligand. Results were expressed as reactivity coefficients (RC), which are the ratios of variants reactive with Con A to the variants not reactive with Con A. No significant differences were found between the mean RC (+/- SD) in healthy individuals (1.35 +/- 0.26) and that in patients with various degrees of SLE activity. In contrast, a significantly higher mean RC was found in sera from patients with intercurrent infection (2.70 +/- 0.76) compared with each of the other groups studied (P less than 0.001). An RC greater than 2.25 was found in none of 42 sera from patients without infection and in 15 of 18 sera from patients with infection (sensitivity 83%, specificity 100%). C-reactive protein (CRP) levels were also significantly higher in SLE patients with intercurrent infection than in patients with very active disease (P less than 0.05). Levels of CRP greater than 60 mg/liter were found in 3 of 42 SLE patients without infection and in 8 of 18 patients with infection (sensitivity 39%, specificity 93%). The results show that in SLE patients, the finding of a relative increase in Con A-bound serum alpha 1-acid glycoprotein is a more sensitive indicator of intercurrent infection than is the finding of increased levels of CRP.