Cyclophosphamide is an antitumor agent that generates evolving cystitis through the release of toxic urinary by-products, mostly acrolein, that attack the bladder walls. Using c-fos expression, which permits quantitative analysis of neural activity, we demonstrated that the paratrigeminal nucleus is involved in processing the inputs that this disease generates. c-Fos staining in the paratrigeminal nucleus increases regularly reaching a plateau over the 4 h postinjection period during which the disease develops. The degree of staining is directly correlated with that of the subnucleus medialis of the nucleus of the solitary tract, which is one of the main structures that processes cystitis-related inputs at the supraspinal level.