Illicit use of stimulant drugs such as methamphetamine, ecstasy, and cocaine is a current and growing problem throughout the world. The aim of the current study was to investigate the long-term effect of illicit stimulant use on human motor cortical and corticospinal circuitry. We hypothesized that individuals with a history of primarily methamphetamine and ecstasy use would exhibit altered corticospinal excitability and intracortical inhibition within motor cortex. The study involved 52 healthy adults (aged 26 ± 7 yr) comprising 26 abstinent stimulant users, 9 cannabis users, and 17 nondrug users. The experiment involved a routine urine drug screen, drug history questionnaire, neuropsychological assessment, and single- and paired-pulse transcranial magnetic stimulation (TMS) over motor cortex. EMG responses to stimulation [motor evoked potentials (MEPs)] were recorded from the contralateral first dorsal interosseus. At a given stimulus intensity, MEP area was significantly larger in abstinent stimulant users than in nondrug users during both relaxation (P = 0.045) and muscle contraction (P < 0.001). MEP latency was also significantly longer in abstinent stimulant users (P < 0.009), and they exhibited significantly greater muscle activity during performance of a given task (P = 0.004). However, resting motor threshold and the response to paired-pulse TMS were unaffected. The results suggest that abstinent stimulant users exhibit long-term changes in the excitability of motor cortical and corticospinal circuitry and muscle activity during movement. These changes may partly underlie anecdotal and objective reports of movement dysfunction in chronic stimulant users.