Staphylococcus aureus protein A (SpA) is shown to induce a temporary chemiluminescence (CL)-response of human peripheral blood mononuclear cells. Maximal activity of SpA is observed at 3 μg/ml and EC50 is about 1 μg/ml. The CL response depends on extracellular calcium, and moreover is inhibited by pretreating cells with rabbit-anti-human IgG's. From glass-adhered monocytes, SpA alone (3 μg/ml) did not consistently affect the generation of immunoreactive interleukin-1 (IL-1). However, SpA and endotoxin (1 μg/ml) showed a marked synergistic effect on IL-1 release. The results suggest that SpA interacts with membrane-bound Ig molecules endowed with receptor functions. The CL response may be envisaged as a result of early transmembrane signalling events presumably taking place in monocytes. Apparently, hereby, the cells become primed for endotoxin-triggered IL-1 release.