The possibility of site-selective substitution of 18O into YBa2Cu3O7 was explored. Samples containing various quantities of 18O were prepared by processing in 18O2 both at 950 °C and at 400 °C. The samples were characterized by secondary ion mass spectroscopy (SIMS), temperature programmed desorption (TPD) and reduction (TPR), Raman spectroscopy, and magnetization measurements. Measurements of the shifts in the Raman active modes with 18O substitution and of the ratios of 18O to 16O by TPD, TPR, and SIMS show that even for temperatures as low as 400 °C and times as short as 2 h. 18O is not substituted exclusively into the chain site (O1) in YBa2Cu3O7. In addition, there is no consistent variation in the shifts in Tc with the degree of substitution; therefore, the isotope effect for a sample with 100% 18O cannot be predicted by a linear extrapolation of data obtained for samples with partial 18O substitution. The mechanism of oxygen substitution, the difficulties of measuring the true magnitude of the oxygen isotope shift, and the meaning of the small isotope shift are discussed.