Superantigens use an elaborate and unique mechanism of T lymphocyte stimulation. Prototype superantigen are the pyrogenic exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes. Many candidate proteins of bacterial, viral and protozoal origin have recently been reported to be superantigens. In most cases the evidence that these proteins are in fact superantigens is highly indirect. In this review the evidence that gram-positive cocci produce superantigens other than the pyrogenic exotoxins is critically discussed. Evidence in described demonstrating that the epidermolytic toxins of Staphylococcus aureus and the pyrogenic exotoxin B and M-proteins of Streptococcus pyrogenes are not superantigens. Criteria are described for acceptance of a candidate as a superantigen.