Minor reactions to streptokinase are not uncommon, although the etiolo
gy is unknown. It is widely presumed, however, that these, like the mo
re serious immune reactions, are antibody-mediated. We measured specif
ic anti-streptokinase IgG, subclasses IgG1, IgG2, IgG3, IgG4 and IgE b
y ELISAs, haemagglutination, indirect Coombs' test and immunoblotting
in six patients who developed reactions to streptokinase. Evidence of
complement activation by streptokinase was sought by a haemolytic comp
lement assay and by measurement of C3, C4 and C3d. The patients who re
acted to streptokinase presented with low titres of anti-streptokinase
IgG (median = 5; range 0-32) and IgG1 (median=3; range 0-14). No evid
ence of any other IgG subclass was found, nor of specific anti-strepto
kinase IgE. Anti-streptokinase IgG1 was found to fix complement; patie
nts who reacted to streptokinase were found to have low levels of tota
l complement 1 year post reaction. Probable aggregates and fragments o
f human albumin (added stabiliser) were found in the streptokinase pre
paration and proved to be antigenic in some patients, but were not fou
nd to be related to the development of reactions. The findings suggest
that patients who develop reactions to streptokinase cannot be predic
ted on the basis of antibody titres at presentation. Minor reactions t
o streptokinase would not appear to be antibody-mediated, although com
plement activation may be involved.