Evidence is emerging that sodium phosphate (NaP), a commonly used oral cathartic agent, causes aphthoid ulcers or focal active colitis (FAC) in the colon and rectum. The aims of this study were (1) to assess the incidence of such ulcers diagnosed endoscopically ("aphthoid ulcers"), (2) to assess the incidence of histologically detected FAC and neutrophilic infiltration overlying lymphoid follicles ("aphthoid lesions"), and (3) to determine whether this effect of NaP is associated with epithelial cell proliferation. Aphthoid ulcers, unexplained by other diagnoses, were found in 18 of 687 consecutive patients (2.6%) who underwent colonoscopic examination after oral NaP preparation during a 12-month period; biopsy specimens showed FAC or aphthoid lesions. FAC was present in 11 of 316 patients (3.5%) who had biopsies but were endoscopically normal. Eight patients with aphthoid ulcers in the rectosigmoid showed no abnormalities when reexamined by flexible sigmoidoscopy after an interval as short as 7 days (range, 7 to 56 days). Mucosal biopsy specimens from these patients were assessed for apoptosis and epithelial proliferation by determining the MIB-1 labeling index (LI). The LI was increased by 136% after NaP preparation (55 +/- 6) compared with biopsy specimens obtained from the same patients during reexamination without NaP preparation (23 +/- 6, P = .01). This correlated with the number of apoptotic bodies per 10 colonic crypts (1.2 +/- 0.3 v 0.5 +/- 0.2, respectively). To determine whether these proliferative changes represent a response to mucosal ulceration, rectosigmoid biopsy specimens were compared in two additional patient groups: an NaP group in whom no gross lesions were evident and a no-NaP group who were not exposed to NaP. Although more modest, similar changes in the LI (42 +/- 4 and 30 +/- 3, respectively, P = .03) and in the occurrence of apoptotic bodies per 10 colonic crypts (1.3 +/- 0.4 and 0.4 +/- 0.1, respectively) were observed. We conclude that use of NaP is associated with increased colorectal crypt epithelial cell proliferation. This proliferative response to NaP exposure is evident in the absence of colonoscopically or other histologically recognizable abnormalities. In a proportion of patients, aphthoid ulcers, FAC, or aphthoid lesions serve as markers of mucosal damage by NaP.