Background: Significant lymphopenia is a prominent feature in systemic erythematous lupus, but has not been described in Wegener’s granulomatosis (WG). We suggest from a retrospective analysis that lymphopenia may also be an index of WG disease activity. Methods: Medical charts form 19 patients diagnosed with systemic active WG between 1990 and 2000 were reviewed retrospectively. All patients had crescentic glomerulonephritis and alveolar hemorrhage. Clinical and biological markers were reviewed at three different time points: diagnosis, time of relapse, and during remission. Results: Average lymphocyte count was significantly lower at diagnosis and relapse than during remission times (p < 0.008 and p < 0.000002, respectively). During disease activity either at diagnosis and during relapses, ANCA titers were highly positive (≧50 IU/ml) in 27.5% of patients (8/29). The corresponding lymphocyte counts were below normal (1,500/min<sup>3</sup>) in 28 of 29 patients (96.5%). In patients with either negative or weakly positive ANCA, mean lymphocyte count was 728.5, 744.2 and 2,551/ml at diagnosis, during relapse and remission times, respectively. There was a clear negative correlation between the lymphocyte count and disease activity. Conclusion: Lymphopenia appears to be a good marker of WG activity. This index might be useful in all patients including those with negative ANCA.