The effect of major surgery, blood loss and psychological stress on the peripheral white blood cell (WBC) populations of human patients and healthy volunteers was examined. During, and in the hours immediately after, major surgery, there was a highly significant fall in the numbers of circulating lymphocytes (mean congruent to 30%-60%) and a highly significant decrease in polymorphs (mean congruent to 160%-350%). Blood loss and psychological stress are not major factors contributing to this fall in peripheral blood lymphocytes in the human, as blood donors and invididuals under temporary stress (anxiety about an imminent dental procedure or an important examination) showed no change in their peripheral blood lymphocyte levels in the hours immediately after these experiences. Significant increases in circulating polymorph numbers, however, accompanied procedures involving even slight tissue trauma, e.g. following blood donation and tooth extraction, but did not occur after psychological stress alone, and were much smaller (congruent to 20%-55%) than those occurring after major surgery. Thus, apart from the complex question of anaesthesia, the nature of the surgical procedure, probably, that is, the degree of tissue trauma involved, is the most important trigger determining changes in the circulating WBC counts after operation.