AbstractLinezolid is a novel oxazolidinone antibiotic that has a spectrum of activity encompassing a variety of Gram‐positive bacteria. The objectives of this study were twofold: (1) to compare the absorption of linezolid tablets given immediately following a high‐fat meal with the absorption of tablets administered while fasting, and (2) to assess the bioavailability of a 375‐mg oral dose given while fasting relative to a 375‐mg dose of linezolid sterile solution given intravenously. Venous blood samples were taken over the 48 h following the single dose administration of both the oral and intravenous (IV) treatment. Samples were subsequently frozen for the determination of linezolid concentrations by HPLC. The only statistically significant difference between the fasted and the fed treatment was in peak plasma concentration, with the mean Cmax for fasted subjects being 23% greater than that for subjects after consumption of a high‐fat meal. Comparable AUC0–∞ values were measured under both conditions, indicating that the overall extent of absorption is the same. Therefore, the difference in Cmax, while statistically significant, should not affect the therapeutic efficacy of linezolid when it is administered with food. There were no statistically significant differences in AUC0–∞, CL or half‐life between the fasted oral treatment and the intravenous treatment. As expected, Cmax was statistically different between the two treatments. However, the mean absolute bioavailability (F) of the tablet, using the IV sterile solution as the reference treatment, was 103% (±20%). Copyright © 2001 John Wiley & Sons, Ltd.