The oncogenic potential of (+/-)-4-diethylamino-1,1-dimethylbut-2-yn-1-yl 2-cyclohexyl-2-hydroxy-2-phenylacetate monohydrochloride monohydrate (NS-21), a new drug for the treatment of urinary frequency and incontinence, was assessed when it was administered in the diet of Charles River Fischer-344 rats for 2 years in dosages of 0, 10, 30 and 100 mg/kg/day. No drug-related effects occurred on survival, appearance or behavior, or occurrence, location or number of palpable masses. Food efficiency and hematologic values also were apparently unaffected. Statistically significantly low mean weekly body weights and average food consumption values were observed in the all dose groups. The plasma concentrations of NS-21 and its active metabolite, RCC-36, in the treated groups were increased in a dose-dependent manner. Histopathological examinations disclosed test article-related increases in the incidence of periportal hypertrophy and midzonal hepatocellular vacuolization in the livers of the 100 mg/kg/day animals. There were no test article-related effects on the incidence or type of neoplastic lesions. In conclusion, under the conditions of this study, no oncogenic effects were evident in Fischer-344 rats when NS-21 was administered in the diet in concentrations to produce an intake of up to 100 mg/kg/day for 2 years.