From February 1988 through October 1988, 23 samples of peritoneal dialysis fluid from 20 patients with end-stage renal disease were cytologically analyzed in an attempt to determine the effect of the dialysate on the mesothelial cells lining the peritoneal cavity. The patients, five female and 15 male, ranging in age from 26 to 75 yr, had been on continuous ambulatory peritoneal dialysis (CAPD) from 1 mo to 6 yr, 4 mo. The patients had no history of cirrhosis, neoplastic disease, radiation and/or chemotherapy, or current findings of infection. Smears and cytosieve filter preparations were made. Smear analysis included the mesothelial cell pattern, the degree of mesothelial cell atypia, and the presence of atypical multinucleated cells and mitoses. In the majority of the fluid samples, reactive mesothelial cells were arranged singly and in sheets. Moderately and severely atypical mesothelial cells were glandular and papillary in configuration. All samples contained at least a few reactive mesothelial cells; in six, the highest degree of cellular atypia was moderate; in 17, it was severe. The development of severe cellular atypia did not appear to be time dependent (a finding noted in samples from patients on dialysis for 6 mo up to 6 yr). When present, multinucleated mesothelial cells showed moderate to severe atypia. In four cases mitotic figures were present. On the basis of these findings, it is proposed that peritoneal dialysis plays a role in the development of mesothelial cell atypia.