Squirrel monkeys responded under a fixed-interval schedule of intravenous cocaine injection that alternated with a fixed-interval schedule of either presentation of electric shock or termination of a stimulus associated with electric shock. As the dose of cocaine was increased from 10 to 1000 microgram/kg/injection, responding maintained by cocaine injection or alternately by electric shock first increased and then decreased. The lowest doses of cocaine that reliably maintained self-administration often increased responding maintained by electric shock; the highest doses of cocaine that continued to maintain self-administration often decreased responding maintained by electric shock. When saline was substituted for cocaine, responding that had previously been maintained by cocaine injection occurred irregularly and at very low rates, whereas rates and patterns of responding maintained by electric shock were characteristic of fixed-interval schedules. When the fixed-interval schedule of cocaine injection was replaced by intravenous injections that occurred without regard to antecedent responding, the effects of cocaine on responding maintained by electric shock were found to be independent of the way in which cocaine was administered.