The effect of food on the relative bioavailability of an erythromycin particles-in-tablet formulation was studied in 27 healthy volunteers, using a four-way, crossover study design with the following treatments: one or two erythromycin capsules USP (Eryc, Parke-Davis), or one polymer-coated erythromycin particles-in-tablet (PCE, Abbott) administered fasting or with a high-fat meal. Under fasting conditions the erythromycin particles-in-tablet and erythromycin capsule formulations are bioequivalent based on similar tmax and dose-normalized Cmax and AUC values. The rate and extent of absorption from the particles-in-tablet formulation, however, are dramatically reduced following administration with a meal. Mean Cmax and AUC values decreased by 73% and 72%, respectively, and seven subjects had no detectable erythromycin plasma concentrations for 16 hours following administration of the particles-in-tablet formulation with the high-fat meal. Greater than 40% of the subjects had nonfasting Cmax and AUC values that were less than 10% of those values following administration of the dose fasting. Cmax and AUC values in nonfasting subjects were within 75% to 125% of fasting values in only two and one of 27 subjects, respectively. The erythromycin particles-in-tablet formulation therefore should not be administered with meals.