The structural requirements for murine P-388 leukemia activity in the dopamine series were investigated. Eight of the 31 analogs evaluated possessed reproducible antitumor activity. The ortho-aromatic hydroxyl groups were required for activity, but the aminoethyl side chain was not crucial since this group could be replaced by methyl or aminomethyl groups with the retention of activity. The lack of activity of O-alkylated and monosubstituted analogs suggests that o-quinone formation may be important for activity, a possibility supported by the observed P-388 activity of 5-hydroxydopamine compared with the inactivity of the 6-hydroxy isomer.