A twenty-eight day repeated oral dose toxicity test of dihepthyl phthalate (DHP) was carried out in male and female F344 rats at the dose levels of 0, 0.2, 1 and 5 g/kg/day. All rats in each group, consisting of 5 males and 5 females, received a daily intragastric administration of DHP for 28 days. Additional two groups of animals exposed to dose levels of 0 and 5 g/kg were used for investigation of subsequent recovery for 2 weeks. No animals died during the administration period. Inhibition of body weight gain was observed in both sexes of the 5 g/kg group. Blood biochemistry revealed significant increases in albumin and A/G ratio in males of the groups treated with 0.2 g/kg or more, and in albumin and total protein in females treated with 1 g/kg or more. In the 5 g/kg group, BUN, GOT, GPT, ALP and Zn was increased in males, and GOT in females. The increases in GOT, GPT and ALP were also observed in males of the 1 g/kg group. Increases in liver and kidney weights were noted in both sexes treated with 1 g/kg or more and in males of the 5 g/kg group, respectively. Testicular weight was decreased in the 5 g/kg group. On histopathological examination, swelling and necrosis of hepatocytes were found in males of the 1 and 5 g/kg groups. Males of the 5 g/kg group showed atrophy of the seminiferous tubules accompanied with loss of spermatogenesis. In the recovery group, similar changes were detected in the testis, but some of the seminiferous tubules showed slight regenerative changes.(ABSTRACT TRUNCATED AT 250 WORDS)