The effect of a high-fat meal on absorption of a 200-mg dose of cefpodoxime proxetil oral suspension was evaluated in 20 healthy, male volunteers in a randomized, two-way crossover study. The concentrations of cefpodoxime in plasma and in urine were determined by sensitive and specific high-performance liquid chromatography methods. The area under the plasma drug concentration-time curve, time to peak concentration, and urinary excretion of cefpodoxime were significantly greater (P Յ 0.05) after administration of cefpodoxime proxetil oral suspension with food than under fasting conditions. However, the difference in the areas under the curve between fed and fasted treatments was only 11%, and application of the two one-sided tests procedure showed bioequivalence between treatments for this parameter. The slight increase in the extent of drug absorption and the slower rate of absorption which results when cefpodoxime proxetil is given with food are unlikely to be of clinical importance.