The authors respond to comments by Freudenthal et al (see NIOSH- 00229744) on a NIOSH study (Ward et al JNCI 83(7):501-506, April 3, 1991; see NIOSH-00200216) which concluded that an excess of bladder cancer in workers at a chemical manufacturing facility was related to exposure to o-toluidine (95534) (OT) and aniline (62533) (AN). In a reexamination of the NIOSH study, Freudenthal et al disagreed with this finding and concluded that several other chemicals used at the facility were more probable candidates as bladder carcinogens. In response to the allegations by Freudenthal et al that NIOSH investigators did not take into account other chemicals present in the manufacturing process, Ward et al reply that evidence concerning both potential exposure to and carcinogenicity of other chemicals present at the facility were considered and that the weight of the evidence favored OT and AN as the etiologic agents for the excess incidence of bladder cancer. With respect to the comment that NIOSH investigators identified OT, AN and hydroquinone (123319) (HQ) as the only potential carcinogens to which workers were exposed, Ward et al point out that their original paper stated that of the major chemicals used in the processes studied, only OT, AN, and HQ had been evaluated as potential carcinogens by the International Agency for Research on Cancer, and only OT was classified as demonstrating sufficient evidence of carcinogenicity in animals. Ward et al also respond to comments concerning exposure to 4-aminobiphenyl (92671) (ABP), a known contaminant of diphenylamine (122394) (DPA) which was used at the facility; exposure to 3-amino-4-ethoxyacetanilide (17026812) which was also used at the facility but not in the department with the bladder cancer excess; possible exposure to other aromatic amines; and the scientific evidence indicating the carcinogenicity of OT and AN. On the issue of contamination of DPA with ABP, the authors respond that, based on the use pattern of DPA and the low level of ABP contamination (less than 100 parts per million), exposure to ABP as a contaminant was less likely to be associated with the bladder cancer excess than the use of 7.2 million pounds of OT annually. The authors conclude that Freudenthal et al failed to develop a well supported case for the other probable carcinogenic chemicals proposed by their reexamination of the original NIOSH investigation. The authors further conclude, based on the toxicological data and information available on the use of chemicals at the facility, that OT and AN are the most likely causes for the excess incidence of bladder cancer.