A number of clinical reports of drug interactions with influenza vaccine have been made. We hypothesized that CYP3A4 activity would decrease following influenza immunization. Fifteen healthy subjects had erythromycin breath tests (ERMBT) and influenza antibody titer hemagglutinin inhibition assay (HIA) before and after receiving influenza vaccine. The mean age of the subjects was 31.9 years (S.D. 10.2). The change in ERMBT following influenza immunization was not significant (mean -4%, S.D. 17%, P=0.25). Influenza immunization does not significantly change CYP3A4 activity. Changes in serum drug concentrations noted previously after influenza immunization are either due to very small changes in CYP3A4 activity or other pharmacokinetic interactions.