Hapten-induced colitis is a widely used model for the study of the intestinal inflammation and for the testing of novel therapies. However, the hapten utilized in this model, trinitrobenzene sulfonic acid, is difficult to obtain in some countries. We therefore compared this hapten to two structurally related haptens to determine if they could be substituted for trinitrobenzene sulfonic acid in terms of inducing chronic colitis in the rat. Rats received one of the three haptens intracolonically, and the severity of colonic inflammation was assessed 3 and 14 days later. Dinitrobenzene sulfonic acid produced colonic inflammation and ulceration that was indistinguishable from that induced by trinitrobenzene sulfonic acid at both time points. On the other hand, dinitrochlorobenzene produced acute colitis (3 days postadministration), but by Day 14 this inflammation had subsided. Dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produced comparable levels of granulocyte infiltration into the colon (as measured by tissue myeloperoxidase activity and histology) at both time points. These studies suggest that for studies of up to at least 2 weeks in duration, dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produce comparable levels of colonic inflammation. Dinitrobenzene sulfonic acid therefore offers a useful and less expensive alternative to trinitrobenzene sulfonic acid.