AIM: To investigate the role of endotoxin in synergy between bacterial toxins associated with sudden infant death syndrome (SIDS). METHODS: Extracellular toxins of 13 isolates of Staphylococcus from SIDS victims and matched healthy infants were tested for lethal toxicity in chick embryos with and without standard endotoxin (used at 1.00 ng/embryo). Endotoxin and toxins from staphylococci were used at dilutions with negligible lethality. RESULTS: Simultaneous injection of non-lethal levels of endotoxin and toxins from 11 of the 13 staphylococcal isolates tested produced lethal toxicity that was 111 to 613% greater than expected by an additive effect alone. This was highly significant and occurred even in the absence of staphylococcal enterotoxins or toxic shock syndrome toxin-1. CONCLUSION: Endotoxin enhancement of staphylococcal toxin lethality could be partly responsible for the clinical outcome in SIDS.