To test the hypothesis that the initial response to corticosteroid treatment makes it possible to predict the further course of patients with polymyalgia rheumatica (PMR), 20 patients with PMR were prospectively given a therapeutic challenge with 15 mg of prednisolone (PDN) per day. The erythrocyte sedimentation rate (ESR), the fibrinogen and the C-reactive protein (CRP) were measured before and after 7 days of therapy. At the end of the challenge, the CRP had normalized in 11 patients (Group I), whereas it had remained elevated in 9 (Group II). The dose of PDN was thereafter tapered according to a strict and standard schedule integrating clinical and laboratory parameters, and was used as the index of disease control. The statistical analysis was made using a generalized linear model. Follow-up ranged from 8 to 60 months with a median of 38 months. With the PDN dose as the end point, Group I showed a significantly better course than Group II (p = 0.014). There were fewer adverse events due to corticosteroid treatment in Group I (3/11) compared to Group II (7/9). We conclude that the CRP initial response to the corticosteroid treatment is a prognostic factor in patients with PMR. Larger studies are needed to confirm these preliminary results.