By manipulating a signaled upcoming cocaine dose, we investigated how the dose just received and the upcoming dose jointly controlled cocaine self-administration. Three rhesus monkeys self-administered cocaine according to a multiple schedule differing in dose following completion of a fixed-ratio response requirement. The larger dose (0.03 or 0.056 mg/kg) was 10-fold higher than the smaller dose (0.003 or 0.0056 mg/kg). Following each infusion, there was an equal probability that the next dose would be large or small. This resulted in four types of signaled transitions: from a small dose to a small dose, small to large, large to large, and large to small. Across conditions the response requirement was increased. At lower ratios, pauses were brief and run rates were controlled by the upcoming dose. At larger ratios, pauses were pronounced, and run rates suppressed, in transitions from a large to a small dose. The behavioral disruption engendered by this transition occurred with both dose combinations. The results suggest that negative discriminable shifts in drug availability disrupt ongoing responding.