In a randomized multicenter trial the efficacy of treatment of active Crohn's disease by means of a liquid defined formula diet (DFD) was tested and compared with a combination of 6-methyl-prednisolone and sulfasalazine. A total of 95 patients participated in the study. By the end of 6 weeks, among 44 patients randomized to drug treatment, 32 showed improvement of the Crohn's disease activity index (CDAI) as compared with 21 of 51 patients receiving oral DFD (p less than 0.05). The proportion of withdrawals in the DFD group (29 of 51) was sevenfold higher than in the drug group (4 of 44). However, most patients (20 of 29) receiving DFD withdrew because of the unpalatability of the liquid diet. Analysis of patients in each group who finished the study showed equal effectiveness of DFD and the drug regimen. In these subsets of patients the CDAI decreased from 280.8 +/- 90.6 to 151.7 +/- 86.5 (DFD) and from 263.7 +/- 86.3 to 129.3 +/- 63.7 (drug), respectively. Improvement of inflammation factors was similar in both groups at the end of the study, although improvement was delayed in the DFD group. In conclusion, our data show a superiority of the drug combination over DFD in the treatment of Crohn's disease under the conditions of this trial. The results do suggest, however, that DFD offers a therapeutic alternative to prednisolone and sulfasalazine in a subgroup of patients, which has to be closer characterized in further studies.