Ampicillin is often used in high oral doses due to its incomplete absorption. The objective of this study was to compare the bioavailability of bacampicillin, a new prodrug of ampicillin which is nearly completely absorbed, to that of high doses of oral ampicillin. Single oral doses of bacampicillin 400 mg or 800 mg and ampicillin 500 mg, 1 g, or 2 g were given to 12 male subjects according to a cross-over design after overnight fasting. The median time after administration till the peak serum level was 0.75 and 1.0 hour with bacampicillin 400 mg and 800 mg respectively, as compared to 1.5, 2.0 and 1.5 hours for the ampicillin doses. The mean of the individual peak serum level after bacampicillin 400 mg, was 7.7 mg/l, which is higher than that after ampicillin 500 mg, 5.2 mg/l, and about the same as that after ampicillin 1 g, 7.6 mg/l. A slightly higher mean peak level was seen after bacampicillin 800 mg, 12.2 mg/l, as compared to ampicillin 2 g, 10.5 mg/l. The absorption rate was highest with bacampicillin, for which 90% of the absorption had occurred 1 hour after administration as compared to 2.5 hours after administration of ampicillin. The relative bioavailability was about 2--3 times higher after bacampicillin as compared to ampicillin. The data imply dose-dependent absorption of oral ampicillin in high doses as there seems to be a less than proportional increase in AUC. The urinary recovery after bacampicillin was 68--75% as compared to 25--41% after ampicillin. Higher doses gave a lower percentage recovery and this phenomenon was more pronounced with ampicillin.