The present study was designed to re-evaluate the chemotactic activity of recombinant tumour necrosis factor (TNF) and lymphotoxin (LT). TNF and LT induced migration of human monocytes across polycarbonate filter in a 90-min assay. Preincubation with FMLP rendered monocytes unresponsive to subsequent exposure to the same chemoattractant. FMLP-desensitized monocytes retained full responsiveness when exposed to TNF as chemotactic stimulus. The converse was observed when monocytes were deactivated specifically to TNF. FMLP receptor antagonists did not interfere with TNF chemotaxis. A monoclonal anti-TNF antibody inhibited the chemotactic activity of recombinant TNF. These results indicate that, under the experimental conditions utilized here, TNF elicits chemotaxis of human monocytes.