Diacetylmorphine (DAM) and 6-acetylmorphine (AM) exhibit virtually identical dose-response and time-action profiles in studies in antinociceptive, excitatory, antidiarrheal and antidiuretic activity after subcutaneous administration to mice. In antinociceptive (Haffner tail clip, phenylquinone writhing and hot plate) and excitatory (Straub tail) tests, both drugs are 3 to 10 times more potent than morphine (M) and reach their peak effect more rapidly than M. Analysis of these data by graded and quantal methods establishes the comparability of the results obtained, while confirming the greater efficiency of the graded method. The durations of action of DAM and AM are shorter than that of M, yielding significant differences in potency estimates based upon peak vs. total effect. DAM and AM are only twice as potent as M in the suppression of prostaglandin E2-induced diarrhea and in antidiuretic activity. These pharmacodynamic studies, along with prior dispositional studies, suggest that the ability of DAM and AM to rapidly cross the blood-brain barrier determines their potency and time-action differences from M in centrally mediated bioassays. In contrast, DAM and AM are only slightly more potent than M in th antidiarrheal and antidiuretic test. These studies support the concept that the pharmacological effects of DAM are mediated principally by metabolically formed AM.