Biosynthetic labeling with [35S]met and immunoprecipitation with anti-C-reactive protein (CRP) antibodies and Staphylococcus aureus indicate that cell surface CRP is produced by lymphocytes. The ability of anti-CRP to reduce NK activity, and the demonstration that 125I-anti-CRP-labeled PBL are found in low-density Percoll fractions associated with large granular lymphocyte (LGL) and NK activity suggest that S-CRP-bearing cells are NK effectors. The production of S-CRP by LGL supports this hypothesis. While lymphocytes were shown to synthesize S-CRP, monocytes produced no detectable S-CRP. The lymphocytes that produce S-CRP apparently do not secrete it; when lymphocyte culture supernatants were tested, no S-CRP was found. This is the first description of extrahepatic synthesis of CRP.