We have evaluated the clinical usefulness of certain diagnostic tests in consecutive patients with pleural effusions, including 12 who had rheumatoid arthritis, nine who had systemic lupus erythematosus, and 39 who had other diseases. Effusions from patients with rheumatoid arthritis and systemic lupus erythematosus differed with respect to glucose level, lactic dehydrogenase activity, and pH. Complement levels differentiated rheumatoid from control effusions but did not segregate rheumatoid from systemic lupus erythematosus. Immune complexes were detected in all the rheumatoid pleural fluids by radioassays using monoclonal rheumatoid factor, C1q, and Raji cells. In most of the fluids, these complexes were reactive in all three assay systems and their levels higher than those found in paired serum samples. In effusions from patients with systemic lupus erythematosus, however, immune complexes were detected mainly by the Raji cell radioimmunoassay, and levels by all three assays were similar to those of paired serum samples.