We believe this case represents a clear example of drug fever, and it appears to be the first report to implicate ketotifen as the responsible agent, confirmed with double rechallenge. The recognition of drug fever is clinically important. Failure to recognize the etiologic relationship between the drug and fever has unnecessary consequences, including extra testing, empiric therapy, and longer hospital stays. We suggest that ketotifen should be considered as a possible cause of fever in allergic patients receiving this drug.