As aircrew performance declines during periods of sustained flight operations (SUSOPs), countermeasures become more important. This study examined the ability of the central nervous system stimulant d-methamphetamine to ameliorate the detrimental effects of a simulated SUSOP on subjective fatigue and cognitive performance. Subjects (N = 25) repeatedly completed three subjective questionnaires and several subtests of the Unified Tri-Service Cognitive Performance Assessment Battery (UTC-PAB) and the Walter Reed Performance Assessment Battery (WR-PAB) during a simulated SUSOP. The scenario consisted of a 9-hr planning session followed by 4 hr of rest and a 14-hr mission. After 6 hr of rest, the 9 hr-4 hr-14 hr work-rest-work pattern was repeated. In a double-blind procedure, 13 subjects were administered 10mg/70kg body weight of d-methamphetamine 4 hr 20 min into the second mission, whereas the other 12 subjects received a placebo. Consistent with our preceding article in this series (Neri, Shappell, & DeJohn, 1992), the aircrew appeared to shift from a conservative to a more risky response strategy as the simulated SUSOP progressed. Administration of d-methamphetamine reduced subjective fatigue, improved performance, and lessened the apparent risky behavior on two spatial memory tasks.