Shiga toxin and the related Shiga-like toxins (SLT), produced by Escherichia coli, can cause hemorrhagic colitis and hemolytic uremic syndrome (HUS). Human intravenous immune globulin (HIVIg) blocks the cytotoxicity of some SLTs in vitro. To examine the ability of HIVIg to modify disease caused by Shiga-like toxin I or Shiga-like toxin II (SLT-I or SLT-II), we injected 3-day-old rabbits intraperitoneally with SLT-containing cell-free supernatants from Escherichia coli O157: H7. A subset of rabbits was treated with subcutaneous HIVIg. All rabbits given 10(4) CD50 of SLT-I developed severe diarrhea, and 5 died. When HIVIg 500 mg/kg was given in addition to SLT-I, only 6 of 18 rabbits (33.3%) developed diarrhea (P < 0.0001), and 1 died. HIVIg 500 mg/kg or 1,000 mg/kg protected against diarrhea when given one hour prior to toxin. HIVIg 1,000 mg/kg was protective when administered one hour after toxin, but not at 6 or 24 hr. Seventeen of 18 rabbits given 10(6) CD50 of SLT-II developed severe diarrhea, and 4 died. In contrast to SLT-I-associated disease, HIVIg had no effect on diarrhea in rabbits given SLT-II. We conclude that HIVIg protects infant rabbits from diarrhea and death caused by intraperitoneally administered SLT-I, but does not affect the course of SLT-II-associated illness.