A human immunodeficiency virus-infected individual developed severe secretory diarrhea due to infection with Staphylococcus aureus. When octreotide therapy was initiated, a toxic shock-like syndrome developed that was associated with fever, multisystem organ damage, and ultimately, desquamation of the palms and soles. The isolate was methicillin susceptible and produced enterotoxins B and C. This is, to our knowledge, the first reported case of toxic shock syndrome to develop secondary to staphylococcal enterocolitis in an adult.