Lipopolysaccharide (LPS) and phorbol esters (TPA) stimulate lymphocytes proliferation in two different ways. While LPS primary function is specific receptor binding, TPA directly activate cellular protein kinase C. The stimulation of human leukaemic lymphocytes (from chronic lymphocytic leukaemia patients) with LPS and TPA results in two different types of response: to both stimulators, and to LPS only. Therefore the supposed defect of cellular receptors can not explain all the observed effects. The existence of TPA independent second messengers and changes in signal transduction pathways downstream of PKC can be considered.