In vitro cellular immunocompetence was investigated on 35 patients with Hodgkin's disease by studying their in vitro lymphocyte responsiveness to full range stimulation achieved by a spectrum of phytohemagglutinin concentrations. When compared to the normal lymphocyte profile elicited from 35 control subjects, the Hodgkin's patterns of response enabled the identification of a quantifiable lymphocyte defect present in most patients regardless of their clinical status. Increasing severity of this defect was found with progression of the disease and was most pronounced in patients with skin anergy and absolute lymphopenia. The marked abnormality observed in patients restudied after intensive therapy returned towards normal in patients achieving a long lasting, unmaintained complete remission. The data suggest the early presence of an intrinsic functional lymphocyte defect, increasing severity of which may lead to progressive immunoincompetence, reflected to vitro by imparied lymphocyte responsiveness and in vivo by skin anergy and ultimately lymphopenia.