A study was made of the role of cytokine-induced neutrophil chemoattractant (CINC), regarded as a member of the interleukin-8 family, in rat experimental colitis induced by trinitrobenzene sulfonic acid and ethanol. Colonic myeloperoxidase (MPO) activity, a marker of tissue neutrophil infiltration, was observed to reach a plateau from 24 h to 1 week following the induction of colitis; tissue CINC levels, as measured by enzyme-linked immunosorbent assay, rose rapidly, peaking at 12 h before the rise in myeloperoxidase activity. The time-course of tissue leukotriene B-4, another chemoattractant, was followed by that of MPO activity. Neutrophil accumulation into tissue in this model would thus appear to be under the control of CINC. Anti-CINC was also noted to inhibit 32.9 to 58.1% of chemotactic activity determined by bioassay during the same period, this being further evidence that CINC is a major chemotactic agent in this model. The present results indicate that CINC may have a crucial role in initiating neutrophil infiltration in experimental colitis.