To investigate the potential action of antacids on prednisone absorption and on prednisolone serum levels, we studied 5 healthy volunteers and 12 patients with chronic active liver disease. Six patients responded to treatment and 6 did not. After administering two 5-mg tablets of prednisone with 60 ml of water, 60 ml of Melox (AlOH 3.75 g/100 ml + MgOH 4.0 g/100 ml), or 60 ml of Aldrox (AlOH 8.0 g/100 ml + MgOH 1.95 g/100 ml), we measured prednisolone by radioimmunoassay. Both peak heights and areas under the serum-concentration curves were significantly reduced when prednisone was administered with antacids. The relative bioavailability of prednisone after prednisone-antacid treatments compared to that after prednisone-water treatment was 74% +/- 13% (p less than 0.05) with Melox and 57% +/- 15% (p less than 0.01) with Aldrox in healthy volunteers. In patients with chronic active liver disease responding to treatment, prednisone bioavailability was 65% +/- 120% (p less than 0.01) and 87% +/- 20%, respectively. Among patients with chronic active liver disease not responding to treatment, this parameter was 76% +/- 12% (p less than 0.05) and 80% +/- 21% (p less than 0.05), respectively. To insure adequate prednisolone levels in patients with chronic active liver disease, prednisone should not be given simultaneously with antacids.