To investigate if leptin shares in vivo activities with interleukin (IL)-6 family cytokines, it was tested in normal mice for the ability, after a single injection, to induce the acute-phase protein serum amyloid A, to potentiate the induction by IL-1 of serum corticosterone and IL-6, and to inhibit the induction by lipopolysaccharide of serum tumor necrosis factor and, after seven daily injections, to cause body weight loss and to change peripheral blood cell counts. At a 0.5 mg/kg dose, leptin caused body weight loss but did not show any of the other activities above. At a dose of 5 mg/kg, which also caused body weight loss, leptin potentiated the induction by IL-1 of serum corticosterone and IL-6 but did not show any other activity. In addition to causing body weight loss, leptin shows only some of the in vivo activities typical of IL-6 family cytokines and only if used at a dose that exceeds the one sufficient to affect body weight. In vivo, leptin seems to chiefly control body weight and not inflammatory or hematopoietic processes.