In a recent study, we showed that the presence of gentamicin in Palacos R or erythromycin plus colistin in Simplex P bone cement did not significantly decrease the fatigue strength of the cement. [J.P. Davies, D.O. O'Connor, D.W. Burke, and W.H. Harris, "Influence of antibiotic impregnation on the fatigue life of Simplex P and Palacos R acrylic bone cements, with and without centrifugation," J. Biomed. Mater. Res., 23, 379-397 (1989)] However, the commercially prepared Palacos R with Gentamicin and AKZ (Simplex P with colistin and erythromycin) which were tested are not approved by the FDA for use in the United States. Because of this, many surgeons in the United States hand mix tobramycin with the cement in the operating room if a case calls for the use of antibiotic-impregnated cement. In this study, we determined the effect of adding 1.2 g of tobramycin to one pack (40 g) of Simplex P powder on the fatigue strength of the cement. The effect of centrifugation on the fatigue strength of Simplex P with the tobramycin added was also assessed. Simplex P was prepared according to the manufacturer's instructions with and without the addition of 1.2 g tobramycin per 40-g pack and with and without centrifugation. Fifteen specimens of each of the four cement preparations were tested in fully reversed tension-compression fatigue at +/- 15 MPa, 2 Hz. The fatigue strength of the uncentrifuged and centrifuged Simplex P was not significantly reduced by the tobramycin. Centrifugation significantly increased the fatigue life of Simplex P both with and without the addition of tobramycin. The fatigue life of the Simplex P with tobramycin was increased by a factor of 8 by centrifugation.