Purified mouse L cell colony-stimulating factor (CSF) and purified iron-saturated human lactoferrin (LF) were assessed for their effects on release of acidic isoferritin-inhibitory activity (AIFIA) from resident peritoneal and spleen macrophages of B6D2F1 mice. Constitutive release of AIFIA was dependent on the number of macrophages conditioning the culture medium. Detection of release of AIFIA required at least 10(4) macrophages/ml, and increased release was noted with increased concentrations of cells. This release was enhanced by CSF and was induced by CSF from concentrations of 10(3) macrophages/ml, from which constitutive release of AIFIA was not detected. Increased concentrations of CSF induced increased release of AIFIA. The inducing effect was removed by pretreating CSF with rabbit anti-L cell CSF serum. LF suppressed the constitutive as well as the CSF-induced release of AIFIA, but results were dependent on the relative concentrations of LF and CSF used. The suppressive effects of LF were removed by pretreating LF with goat anti-human LF. Constitutive, but not CSF-induced, release of AIFIA could be ablated by removal of Ia antigen-positive macrophages with low concentrations of monoclonal anti-Ia plus complement. Treating macrophages with higher concentrations of anti-Ia in the absence of complement blocked the LF suppression of constitutive AIFIA release but not the CSF-induction of AIFIA release. Release of AIFIA from mouse macrophages can be modulated by CSF and LF. This modulation may be of significance for the regulation of myelopoiesis.