Neutrophil attractant/activation protein-1 (NAP-1 [interleukin-8]) is an 8,400 D protein that is a chemoattractant and granule release stimulus for neutrophils. NAP-1 was first purified from culture fluids of lipopolysaccharide-stimulated human blood mononuclear leukocytes. It was subsequently isolated from lipopolysaccharide-stimulated lung macrophages, mitogen-stimulated lymphocytes, and virus-infected fibroblasts. Interleukin-1 or tumor necrosis factor induces NAP-1 mRNA in many cells, including monocytes, fibroblasts, and endothelial cells. NAP-1 belongs in a family of host defense small proteins, which have a degree of sequence and structural similarity. Noteworthy are the four half-cystine residues in each protein, which are in register when the protein sequences are suitably aligned. Based on cloning data and N-terminal sequence analyses, NAP-1 is secreted as a 79 residue protein after cleavage of a 20 residue signal peptide. The commonly isolated 77 and 72 residue forms are probably extracellular cleavage products. NAP-1 has considerable charge heterogeneity. Charge and length variants all have chemotactic activity. In contrast to many chemoattractants, NAP-1 does not attract monocytes. Intradermal injection of NAP-1 causes neutrophil infiltration. The wide spectrum of cell sources and production stimuli suggests that NAP-1 mediates neutrophil recruitment in host defense and disease.