We have reviewed our data from 55 patients with Crohn's disease (CD) treated with alternate-day prednisone (average dose: 25 mg every other morning) between 1966 and 1989 for a mean duration of 6.6 yr. Daily divided corticosteroid doses were given to all patients with active disease that had not been responsive to supportive measures and, in almost all cases, not responsive to sulfasalazine alone. After initial remission was achieved, patients were switched to alternate-day doses. Treatment evaluations utilized global assessment and the CD activity index of Harvey and Bradshaw (CDAI-HB) shown to correlate closely with the National Cooperative Crohn's Disease Study (NCCDS) activity index (CDAI). CDAI-HB scores of 0-1 indicated no or minimal activity, whereas scores of 2-15 indicated progressive activity. With the CDAI-HB and global assessments, in agreement in all cases, 33 patients (60%) showed favorable responses with 95% confidence intervals (CI) of 46.8 to 73.2. Comparing the results with a literature-based 20% spontaneous longterm remission rate, the data are significant at p < 0.01. Serious complications were gratifyingly low, with no observed instances of osteonecrosis. It is concluded that alternate-day prednisone treatment and treatment maintenance, with or without concomitant sulfasalazine, after conventional induction of remission with daily steroid doses, is a reasonable treatment option for patients with CD not responsive to sulfasalazine alone.