In a step-up approach of DMARD treatment of RA a fast response and an early DMARD switch in the case of non-response is important. Therefore, we performed an open trial in which we compared an 8-week and a 16-week observation period during treatment of RA with MTX or LEF, both given in intensified starting doses and accompanied by moderate dose prednisone. MTX and LEF naïve patients with RA (mean time since diagnosis: 2.3 years) were randomised to receive either LEF in a 3-day-loading dose of 100 mg/day followed by 20 mg/day (n = 19) or MTX intramuscularly in a dose of 25 mg once weekly (n = 21). All patients received concomitant treatment with oral prednisone in an initial dose of 20 mg/day with weekly dose reductions of 5 mg/day. The disease activity was re-evaluated 8 and 16 weeks after the start of the treatment. Mean DAS28 before the start of treatment was 5.36 +/- 0.8 for the MTX-group and 5.46 +/- 0.8 for the LEF-group. After 8 weeks of treatment the DAS28 in the MTX-group was 2.59 +/- 1.0 and 3.16 +/- 0.8 in the LEF group (difference not significant). The mean DAS28 at re-evaluation 16 weeks after the starting of treatment (2.58 +/- 1.5 for the MTX-group and 3.25 +/- 1.16 for the LEF-group) was significantly different neither in between the both treatment groups nor in comparison to the week 8 evaluation. Efficiency of RA treatment with MTX or LEF in intensified doses and in combination with moderate dose prednisone can be sufficiently judged 8 weeks after its initiation.