Bovine lactoferrin (BLF) given into mice, sensitized to SRBC, together with the eliciting dose of antigen, inhibits very strongly the DTH reaction measured after 24 h by foot pad swelling. Administration of BLF at 48 or 24 h before eliciting the DTH reaction was not effective, however, BLF suppressed the reaction when given at the peak of the inflammatory process. The effects of BLF were strongest when the protein was injected intravenously. Intraperitoneal or intramuscular administrations of BLF were less inhibitory. In addition, BLF diminishes, although to a much lesser degree, the inflammatory reactions induced by BCG. The inhibitory action of BLF does not involve liver since treatment of mice with galactosamine does not reverse the inhibition. Studies on cytokine production revealed that peritoneal macrophages, derived from mice pretreated with LF, have an increased ability to produce in vitro IL-6 after induction with LPS. In addition, we demonstrated that inhibition of macrophage migration, mediated by migration inhibition factor, is abolished by BLF. Lastly, the inhibitory effect of BLF could not be transferred with serum from donors treated with BLF. In summary, the data reveal the inhibitory properties of LF, administered systematically, in relation to locally induced inflammation.