Despite the recent rise in oral methylphenidate (MPH) abuse, few studies have characterized the time course of oral MPH brain effects in human subjects. Accordingly, this study assessed the hemodynamic effects of oral MPH effects in 11 healthy young adults (six women), by measuring brain transverse relaxation times (T2). T2 can be interpreted as a surrogate marker for, and inversely correlated with, steady-state cerebral blood volume (CBV). Data were acquired from the caudate nucleus, putamen, and thalamus, using a 1.5 T MRI scanner at baseline and serially for 2 h following oral MPH administration (0.5 mg/kg). Physiological and subjective measures and plasma MPH levels also were examined. MPH induced a selective T2 decrease (-1.65+/-0.53 ms) in the putamen (F(6,54)=2.68, P<0.03). Heartrate, blood pressure and plasma MPH levels increased significantly after drug administration, as well as subjective ratings of "feeling drug effect". T2 decreases may reflect MPH-induced increases in putaminal blood volume. These data suggest that T2 relaxometry can be used to study the time course of regional cerebral blood volume responses to MPH and perhaps to other stimulant drugs.