Because no systematic analysis of drug fever has been done, there has been no means for testing the validity of published characterizations of this clinical entity. We reviewed the clinical characteristics of 51 episodes of drug fever in 45 patients hospitalized at two Dallas hospitals between 1959 and 1986, and 97 episodes reported in the English literature between 1966 and 1986. Unlike characterizations found in textbooks and review articles, we found relative bradycardia in a minority of cases reviewed; little risk associated with rechallenge unless underlying cardiovascular disease was present; no characteristic fever pattern; a highly variable lag time between the initiation of the offending agent and the onset of fever; an infrequent association with either rash or eosinophilia; and no apparent association of drug fever with systemic lupus erythematosus, atopy, female sex, or advanced age.