The absorption of orally administered nafcillin sodium monohydrate buffered with calcium carbonate was studied in 10 healthy human volunteers. Dosages of 500 mg and 1 g were studied in fasting and nonfasting states. There was considerable individual variation in the absorption of nafcillin, although measurable serum concentrations were obtained in all subjects. With few exceptions, peak serum concentrations were reached faster and were more predictable in the fasting state than in the nonfasting state. In the majority of subjects, food interfered with nafcillin absorption. Measurable serum concentrations persisted for 4 h in almost all subjects, but there were no or negligible serum concentrations at 6 h. The mean serum concentrations obtained in the present study were higher than those reported in an earlier study.