Objective To investigate the effect of heroin dependence on the expression of adrenocorticotrophic hormone （ACTH） in ACTH positive cells of pars distalis hypophyseos and the level of serum cortisol for exploring the possible mechanism of the changes. Methods Fifty-five adult male SD rats were randomly divided into a normal control group (NCG),a saline control group (SCG) and a heroin dependence group (HDG). Heroin-dependent rat models were set up by the way of subcutaneous injection of heroin and the hypophysis were excised on the 10th, 17th, 24th, 31st and 38th days after models were set up.Immunohistochemical SABC method, imagine analysis and radioimmunoassay(RIA) were used in the research. Results Compared with the NCG and SCG, the immune staining intensity of ACTH cells in HGD was weakened. The average gray value was significantly higher ( EM>P/EM><0.05 ).The result of RIA showed that the level of serum cortisol in HDG decreased as compared with the NCG( EM>P/EM>﹤0.05 ). Conclusion During heroin dependence, the expression of ACTH positive cells diminished, the level of serum cortisol reduced. The morphological and functional changes suggest that the heroin inhibits the function of the pituitary-a