The galactoside-specific plant lectin, Viscum album agglutinin-(VAA)-I has been shown to activate the natural immune system and modulate the maturation of thymocytes in vivo. However the mechanism of this immunobiological action is not yet understood. In our previous study we demonstrated the VAA-I-induced enhancement of proliferation and selection of thymocytes which inhibited the dexamethasone (DX)-induced thymocyte depletion. In this present work we investigated the effect of 1, 4 and 21 days of VAA-I treatment on DX-induced apoptosis of thymocytes in Balb/c mice. The number of early apoptotic cells was detected with Annexin V staining while the late apoptotic cells were identified according to their propidium iodide incorporation into DNA using flow cytometry. The expression of glucocorticoid receptor (GCR) in double-negative (DN), double-positive (DP) and CD4 or CD8 single-positive (SP) cell populations was assessed. The additive effect of lectin on DX-induced apoptosis of thymocytes consisted of two different actions of VAA-I and DX. One-day VAA-I treatment caused enhanced apoptosis in SP mature cells in contrast to the apoptotic effect of DX, which was mainly directed towards immature DN and DP cells. Treatment with 30 ng/kg VAA-I for four days elevated the GCR level (mean fluorescence intensity) in DP thymocytes. Lectin treatment for 21 days caused more than 20% elevation of GCR expression in all thymocyte subpopulations (DN, DP, CD4+ and CD8+). These results suggest that VAA-I may alter the sensitivity of thymocytes to glucocorticoids and this effect may play a role in the bell-shaped dose-response curve of lectin-induced immunological effects.