The acute toxicity (in rabbits and rats) and the subchronic and chronic toxicities (in rats) of Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a potentially useful pharmaceutical excipient, were investigated. 1) In the acute toxicity study (single oral dose of 2.5 g/kg), no deaths or behavioral abnormalities were observed. Thus, LD50 is higher than 2.5 g/kg. 2) In the subchronic toxicity study (0.63, 1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 2 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in rats of both sexes, but the effect was not statistically significant. 3)In the chronic toxicity study (1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 6 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in male rats, but it was not statistically significant. 4)Various biochemical and physiological abnormalities in rats were noted in all groups (including the control groups) in the toxicity studies, but there appeared to be no significant dose-related finding attributable to the administration of HPMCAS.