Canine systemic lupus erythematosus (SLE) is a disease clinically very similar to its human counterpart. But so far, no study has reported an accurate evaluation of the lymphocyte subsets in the canine disease. Here, we present a study in which lymphocyte subsets have been evaluated in the peripheral blood of 20 dogs suffering from spontaneous systemic lupus erythematosus (SLE) in active and inactive phases, before and during treatment with prednisone and levamisole. 22 healthy dogs have been used as a control population. We show that canine SLE in active phases is associated with a several lymphopenia (1050 +/- 520 10(6) cells/l versus 2130 +/- 1 020 10(6) cells/l in controls). A striking finding is the imbalance of the CD4 and CD8 subsets (respectively 56.7 +/- 10.7% and 10.9 +/- 3.8% of CD4+ and CD8+ lymphocytes versus 40.5 +/- 11.5% and 18 +/- 4.4% in controls) and a strong activation of T-cells in active phases (64.1 +/- 16.9% of 2B3+ cells versus 46.5 +/- 16.7%). Moreover, we observed a persistence of the T subset imbalance during spontaneous evolution. In contrast, the treatment induced in dogs showing a good response the correction of CD4/CD8 ratio and no clinical manifestations, whereas in low responders no such improvements were observed. Thus, this work suggests that the main immunological imbalance seen in SLE could be associated with defective suppressor cells and provides further evidence of similarity of human and dog SLE.