Sera from twenty-one patients with systemic lupus erythematosus (SLE) were analysed for the presence of circulating soluble immune complexes by a sensitive and quantitative radioimmunoassay employing radioiodinated human Clq (Clq-deviation test). In twenty-five normal individuals the percentage of Clq inhibition was 2-64 +/- 4-45%. Eleven of the SLE patients had significantly elevated values, and the mean value for the group was 20-38 +/- 20-64%. The seven patients with renal disease had somewhat higher levels (24-14 +/- 18-70%) than those without kidney involvement (19-00 +/- 21-84%), and elevated levels of antibodies to native DNA also were associated with high levels of percentage of Clq inhibition. Both intermediate (7S-19S) and large (greater than 19S) complexes were present in the sera, and digestions with DNase and RNase indicated that antibodies to DNA and RNA accounted for only some of them. Serial studies in individual patients demonstrated the assocation of circulating complexes with, and often preceding, falling complement levels during disease activation.