Trimethylolpropane triacrylate (TMPTA) is used as an ingredient in a wide variety of coatings, resins, photosensitive materials, and superabsorbent baby diapers. We studied the effects of TMPTA on male and female rats and mice to identify potential toxic or cancer-related hazards. We applied solutions containing TMPTA in acetone on the backs of male and female rats and mice. Groups of 50 male and female rats and mice received 0.3, 1, or 3 milligrams of TMPTA per kilogram of body weight five days per week for two years. Groups of animals receiving acetone alone served as the control groups. At the end of the study, tissues from more than 40 sites were examined for every animal. Survival and body weights of all groups of exposed animals were similar to the control groups. Epidermal hyperplasia was observed in the skin at the site where the chemical was applied in all groups of animals receiving 1 mg/kg or more. Hyperkeratosis at the site of application was also increased in rats receiving TMPTA, and chronic inflammation was also seen in the skin of male and female mice receiving TMPTA. Malignant mesotheliomas were seen in a few male rats exposed to TMPTA. Two different rare forms of liver cancer (hepatoblastoma and hepatocholangiocarcinoma) were observed in some of the female mice exposed to TMPTA, and tumors of the uterus (stromal polyp or stromal sarcoma) also occurred in some exposed female mice. We conclude that exposure to TMPTA caused rare cancers of the liver and tumors of the uterus in female mice and may have been related to the occurrence of malignant mesothelioma in male rats. No occurrences of cancer were associated with exposure to TMPTA in female rats or male mice. Skin lesions at the site of application, including hyperplasia in rats and mice, hyperkeratosis in rats, and inflammation in mice occurred in all animal groups exposed to higher concentrations of TMPTA.