Both IL-4 and IL-10 have been shown in vitro to inhibit leukemia cell secretion of IL-1beta, GM-CSF, and TNFalpha, and increase leukemia cell release of IL-1ra. In this study, we have investigated the in vivo effects of IL-4, IL-10, and amifostine on cytokine production in patients with acute myelogenous leukemia (AML). Serum IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF levels were measured in AML patients who received IL-4, IL-10, or amifostine. No significant changes in the serum levels of IL-1ra, IL-1beta, TNFalpha, GM-CSF, and SCF were found in AML patients who received amifostine. Both IL-4 and IL-10 were found to increase serum IL-1ra. This data is in accord with the in vitro studies. However, IL-4 increased serum GM-CSF levels and IL-10 increased serum IL-1beta and TNFalpha levels. These in vivo effects of the two cytokines differ from their in vitro effects. Despite the similar effects of IL-4 and IL-10 on cytokine production by AML cells in vitro, different effects were observed in AML patients in vivo. IL-4 increased serum SCF levels, whereas IL-10 decreased serum SCF levels. IL-4 increased serum GM-CSF levels, whereas IL-10 had no effect on them. Although IL-10 increased serum IL-1beta and TNFalpha levels, IL-4 had no effect on them. These findings indicate that the in vitro effects of IL-4 and IL-10 do not necessarily reflect their in vivo effects, and that the complex effects of the two cytokines on serum cytokine levels make it difficult to predict their therapeutic potential.