Aims  To evaluate the effect of the CYP1A2*1C and CYP1A2*1F polymorphisms on the inducibility of CYP1A2 by omeprazole in healthy subjects.Methods  Mutations of CYP2C19 and CYP1A2 were identified by PCR‐RFLP. Omeprazole, 120 mg day−1, was given to 12 extensive metabolizers (EM) with respect to CYP2C19 (six CYP1A2*1F/CYP1A2*1F and six CYP1A2*1C/CYP1A2*1F of CYP1A2) for 7 days. CYP1A2 activity was determined on three occasions, namely on day 1, day 9 and day 16 using the caffeine plasma index (the ratio of the concentrations of paraxanthine to caffeine), 6 h after oral administration of 200 mg caffeine.Results  There was a significant difference (P = 0.002) between the caffeine ratios for CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes on day 9, but not on day 1 or day 16 (P > 0.05). The changes in the ratios from day 9 to day 1 (48% ± 20%vs 19% ± 20%) and from day 9 to day 16 (50% ± 31%vs 15% ± 22%) were significantly different (P < 0.05) between the CYP1A2*1F/CYP1A2*1F and CYP1A2*1C/CYP1A2*1F genotypes.Conclusion  The CYP1A2*1C and CYP1A2*1F genetic polymorphisms influenced the induction of CYP1A2 activity in vivo by omeprazole.