Serum from a patient with an IgM-lipoprotein cryoglobulin, both before and after removal of the cryoprecipitate at 0 degrees C, had extremely low levels of whole complement (C), C1, C4 and C2, while amounts of the remaining components were normal or only slightly reduced. The cryopredipitate, when added to fresh normal human serum, reproduced this pattern of C fixation. Separation of the patients's serum at 37 degrees C into its lipoprotein, IgG and IgM fractions revealed that the IgM alone would precipitate at 0 degrees C. This precipitation was unaffected by the patients's IgG, but was markedly enhanced by extremely small amounts of the patient's d less than 1-075 lipoprotein fraction or of homologous very low density lipoprotein (VLDL). Aggregation occurred even at 37 degrees C in the presence of VLDL. Fixation of semi-purified human C1 paralleled these results closely: it occurred with the patient's IgM alone at 0 degrees but not at 37 degrees C, while IgM in the presence of the patient's lipoprotein, or of VLDL from normal serum, fixed C1 strongly at 37 degrees as well as at 0 degrees C. Fab dimers and monomers prepared from the patient's IgM did not aggregate in the cold, even in the presence of lipoprotein, and did not inhibit the aggregation of intact IgM in the presence of VLDL, at any temperature. All three highly purified IgM cryoglobulins, and three of four IgG cryoglobulins, fixed C1 strongly. The IgG preparation which failed to fix C1 was the only one which had lost its cryoprecipitability during purification. Measurement of C3 or whole C levels may be an insensitive method for detecting C fixation in cryoglobulinaemia. It is suggested that analysis for C1, C4 or C2 should be employed instead.