Activation events induced by lectins in human lymphocyte cultures differed not only in time kinetics of their appearance but were also in a different manner inhibited by hydroxyurea (HU). 4F2 and Tac expression, thermostable sheep erythrocyte rosette formation, cell volume distribution changes and the enhancement of the purine metabolic rate [( 3H]adenine incorporation) induced by PHA, Con A or PWM were not influenced by HU treatment, suggesting G1-phase dependency of these markers. The decrease in the mitogen-induced marker expression after 48 h of incubation with HU can be explained by the unability of activated cells to process the cell cycle, to divide and to become newly positive cells. Mitogen-induced RNA synthesis was partially, DNA synthesis, PWM-induced Ig synthesis and lectin-mediated HLA class II antigen expression were totally inhibited by HU. It holds especially for the DR antigen that its appearance in a polyclonal model of lymphocyte activation occurs in a later (postmitotic G1) phase of the cell cycle. The inhibitory effect of HU on late activation parameters could be removed after washing the cells. Mitogen-activated, HU-treated PBL cultures after removing HU continued cell cycle progression without requirement for further addition of lectin.